Neutral Fragments Research Articles

Isotope-coded derivatization with designed Girard-type reagent as charged isobaric mass tags for non-targeted profiling and discovery of natural aldehydes by liquid chromatography-tandem mass spectrometry

Aldehyde-containing metabolites are reactive electrophiles that have attracted extensive attention due to their widespread occurrence in organisms and natural foods. Herein we described a newly-designed Girard's reagent, 1-(4-hydrazinyl-4-oxobutyl)pyridin-1-ium bromide (HBP), as charged tandem mass (MS/MS) tags to facilitate selective capture, sensitive detection and semi-targeted discovery of aldehyde metabolites via hydrazone formation. After HBP labeling, the detection signals of the test aldehydes were increased by 21–2856 times, with the limits of detection were 2.5–7 nM. Upon isotope-coded derivatization with a pair of labeling reagents, HBP-d0 and its deuterium-labeled counterpart HBP-d5, the aldehyde analytes were converted to hydrazone derivatives, which generated characteristic neutral fragments of 79 Da and 84 Da, respectively. The isobaric HBP-d0/HBP-d5 labeling based LC-MS/MS method was validated by relative quantification of human urinary aldehydes (slope=0.999, R2 > 0.99, RSDs ≤ 8.5%) and discrimination analysis between diabetic and control samples. The unique isotopic doubles (Δm/z = 5 Da) by dual neutral loss scanning (dNLS) provided a generic reactivity-based screening strategy that allowed non-targeted profiling and identification of endogenous aldehydes even amidst noisy data. The LC-dNLS-MS/MS screening of cinnamon extracts led to finding 61 possible natural aldehydes and guided discovery of 10 previously undetected congeners in this medicinal plant.

Physicochemical properties and anti-inflammatory and immunomodulatory effects of Shengfupian polysaccharides

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 μg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 μg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 μg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1β and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.

Cryogenic Chemistry and Quantitative Non-Thermal Desorption from Pure Methanol Ices: High-Energy Electron versus X-Ray Induced Processes.

X-Ray irradiation of interstellar ice analogues has recently been proven to induce desorption of molecules, thus being a potential source for the still-unexplained presence of gaseous organics in the coldest regions of the interstellar medium, especially in protoplanetary disks. The proposed desorption mechanism involves the Auger decay of excited molecules following soft X-ray absorption, known as X-ray induced electron-stimulated desorption (XESD). Aiming to quantify electron induced desorption in XESD, we irradiated pure methanol (CH3 OH) ices at 23 K with 505 eV electrons, to simulate the Auger electrons originating from the O 1s core absorption. Desorption yields of neutral fragments and the effective methanol depletion cross-section were quantitatively determined by mass spectrometry. We derived desorption yields in molecules per incident electron for CO, CO2 , CH3 OH, CH4 /O, H2 O, H2 CO, C2 H6 and other less abundant but more complex organic products. We obtained desorption yields remarkably similar to XESD values.

Excitation and fragmentation of the dielectric gas C4F7N: Electrons vs photons.

C4F7N is a promising candidate for the replacement of sulfur hexafluoride as an insulating medium, and it is important to understand the chemical changes initiated in the molecule by collision with free electrons, specifically the formation of neutral fragments. The first step of neutral fragmentation is electronic excitation, yet neither the absorption spectrum in the vacuum ultraviolet (VUV) region nor the electron energy loss spectrum have previously been reported. Here, we experimentally probed the excited states by VUV photoabsorption spectroscopy and electron energy loss spectroscopy (EELS). We found that the distribution of states populated upon electron impact with low-energy electrons is significantly different from that following photoabsorption. This difference was confirmed and interpreted with ab initio modeling of both VUV and EELS spectra. We propose here a new computational protocol for the simulation of EELS spectra combining the Born approximation with approximate forms of correlated wave functions, which allows us to calculate the (usually very expensive) scattering cross sections at a cost similar to the calculation of oscillator strengths. Finally, we perform semi-classical non-adiabatic dynamics simulations to investigate the possible neutral fragments of the molecule formed through electron-induced neutral dissociation. We show that the product distribution is highly non-statistical.

Fingerprinting fragments of fragile interstellar molecules: dissociation chemistry of pyridine and benzonitrile revealed by infrared spectroscopy and theory.

The cationic fragmentation products in the dissociative ionization of pyridine and benzonitrile have been studied by infrared action spectroscopy in a cryogenic ion trap instrument at the Free-Electron Lasers for Infrared eXperiments (FELIX) Laboratory. A comparison of the experimental vibrational fingerprints of the dominant cationic fragments with those from quantum chemical calculations revealed a diversity of molecular fragment structures. The loss of HCN/HNC is shown to be the major fragmentation channel for both pyridine and benzonitrile. Using the determined structures of the cationic fragments, potential energy surfaces have been calculated to elucidate the nature of the neutral fragment partner. In the fragmentation chemistry of pyridine, multiple non-cyclic structures are formed, whereas the fragmentation of benzonitrile dominantly leads to the formation of cyclic structures. Among the fragments are linear cyano-(di)acetylene˙+, methylene-cyclopropene˙+ and o- and m-benzyne˙+ structures, the latter possible building blocks in interstellar polycyclic aromatic hydrocarbon (PAH) formation chemistry. Molecular dynamics simulations using density functional based tight binding (MD/DFTB) were performed and used to benchmark and elucidate the different fragmentation pathways based on the experimentally determined structures. The implications of the difference in fragments observed for pyridine and benzonitrile are discussed in an astrochemical context.

Dissociation of N2 by electron impact in electric and magnetic RF fields

Rate coefficients for electron impact dissociation of the N2 molecule under the influence of crossed radio-frequency (RF) electric and magnetic fields were calculated for field frequencies of 13.56, 100 and 200 MHz and for root mean square values of the reduced electric field strength of 300 and 500 Td. The root mean square values of the reduced magnetic field were varied from 0 to 2000 Hx. ?he effects of the strength of the RF fields and their frequency on the rates for the dissociation to neutral fragments and for the dissociative ionization are discussed. The temporal evolution of the rate coefficients during one period of the RF field is shown and discussed.

Multiphoton breakdown of acetylene; formation of organic building block fragments.

Mass resolved REMPI spectra and electron and ion velocity map images were recorded for REMPI of acetylene in the case of two-photon resonant excitations to low lying 3p and 4p Rydberg states. Combined data analysis of ion signal intensities and electron and ion kinetic energy release distribution revealed multiphoton-fragmentation processes in terms of photodissociation and photoionization channels to form the molecular ion, C2H2+ and the fragment ions H+, C+, CH+, CH2+, C2+ and C2H+. The ratio of fragment ion formation over the parent ion formation increases with excitation energy. To a large extent, multiphoton-fragmentation involves the initial breakdown of the molecule into ground and excited state neutral fragments by two-, three- and four-photon dissociation processes prior to multiphoton ionization. The three-photon dissociation processes via superexcited molecular state(s) are found to be the most important and electronically excited fragment species playing a significant role in the overall multiphoton-fragmentation. Furthermore, the data are indicative of the involvement of secondary photodissociation processes and provide information on fragment energetics as well as state interactions. The question, whether acetylene could be an important source of building block fragments for the formation of organic molecules in interstellar space, is addressed.

Photofragmentation specificity of photoionized cyclic amino acids (diketopiperazines) as precursors of peptide building blocks.

The photoionisation and photofragmentation of the two cyclic dipetides cyclo(alanyl-glycine) cGA and cyclo(glycyl-glycine) cGG, have been studied combining experiments and simulations. State selected fragments from the ionized molecules are detected using photo-electron photo-ion coincidence (PEPICO) measurements and specific fragmentation paths are identified and characterized via the use of ion-neutral coincidence maps. The simulations, performed using Quantum Chemistry methods, allow us to infer the fragmentation mechanisms of the ionized and excited molecules. We show that ring opening is followed by emission of the neutral fragments CO and HNCO. In the case of cGG the emission of neutral CO leads to a metastable structure that breaks producing small cationic fragments. The studied cyclic dipeptides evolve under ionizing radiation generating different small aziridin moieties and oxazolidinones. These two species are key reactants to elongate producing peptide chains. The corresponding mechanisms have been computed and show that the reaction requires very low energy and may occur in the presence of ionizing radiation.

Time-Resolved Imaging of High Mass Proteins and Metastable Fragments Using Matrix-Assisted Laser Desorption/Ionization, Axial Time-of-Flight Mass Spectrometry, and TPX3CAM.

The Timepix (TPX) is a position- and time-sensitive pixelated charge detector that can be coupled with time-of-flight mass spectrometry (TOF MS) in combination with microchannel plates (MCPs) for the spatially and temporally resolved detection of biomolecules. Earlier generation TPX detectors used in previous studies were limited by a moderate time resolution (at best 10 ns) and single-stop detection for each pixel that hampered the detection of ions with high mass-to-charge (m/z) values at high pixel occupancies. In this study, we have coupled an MCP-phosphor screen-TPX3CAM detection assembly that contains a silicon-coated TPX3 chip to a matrix-assisted laser desorption/ionization (MALDI)-axial TOF MS. A time resolution of 1.5625 ns, per-pixel multihit functionality, simultaneous measurement of TOF and time-over-threshold (TOT) values, and kHz readout rates of the TPX3 extended the m/z detection range of the TPX detector family. The detection of singly charged intact Immunoglobulin M ions of m/z value approaching 1 × 106 Da has been demonstrated. We also discuss the utilization of additional information on impact coordinates and TOT provided by the TPX3 compared to conventional MS detectors for the enhancement of the quality of the mass spectrum in terms of signal-to-noise (S/N) ratio. We show how the reduced dead time and event-based readout in TPX3 compared to the TPX improves the sensitivity of high m/z detection in both low and high mass measurements (m/z range: 757-970,000 Da). We further exploit the imaging capabilities of the TPX3 detector for the spatial and temporal separation of neutral fragments generated by metastable decay at different locations along the field-free flight region by simultaneous application of deflection and retarding fields.

Metabolites Identification and Mechanism Prediction of Neobavaisoflavone In Vitro and In Vivo of Rats through UHPLC-Q-Exactive Plus Orbitrap MS Integrated Network Pharmacology

Neobavaisoflavone is an important isoflavone component isolated from Psoraleae Fructus. It is used extensively worldwide because of its antibacterial, antioxidant, anti-inflammatory, anticancer, and anti-osteoporotic activities. However, there is no systematic and comprehensive research on the metabolism of neobavaisoflavone in vivo and in vitro. The study aimed to analyze the metabolic characteristics and mechanism of neobavaisoflavone for the first time. Firstly, biological samples were pretreated by the solid-phase extraction (SPE) method, methanol precipitation, and acetonitrile precipitation. Secondly, the samples were analyzed on UHPLC-Q-Exactive Plus Orbitrap MS. Thirdly, metabolites were tentatively identified based on retention time, parallel reaction monitoring strategy, diagnostic product ions, and neutral loss fragments. A total of 72 metabolites of neobavaisoflavone were tentatively identified, including 28 in plasma, 43 in urine, 18 in feces, six in the liver, and four in the liver microsome. The results suggested that neobavaisoflavone mainly underwent glucuronidation, sulfation, hydroxylation, methylation, cyclization, hydration, and their composite reactions in vivo and in vitro. In addition, nine active components with high bioavailability and 191 corresponding targets were predicted by the Swiss Drug Design database. The 1806 items of GO and 183 KEGG signaling pathways were enriched. These results showed that metabolites expanded the potential effects of neobavaisoflavone. The present study would provide the scientific basis for the further exploitation and application of neobavaisoflavone.

Identification of complementary McLafferty rearrangement ions at m/z 222 and 224 of methylstearate using high-resolution electron ionization time-of-flight mass spectrometer

All fragment ions observed in high-resolution electron ionization (EI) mass spectra of methyl stearate have been completely classified into three different series, such as methyl ester (CnHmO2), aliphatic hydrocarbon (CnHm) and acylium (CnHmO) ions. From the EI mass spectra classified into aliphatic hydrocarbon series, complementary McLafferty rearrangement (compMcLR) ion at m/z 224 and complementary McLafferty rearrangement+1 (compMcLR+1) ion at m/z 222 were identified from the standpoints of notable intensity and rearrangement reactions. The fragmentation of the keto- and enol-form molecular ions M.+ was discussed on the basis of the sites of unpaired electron (radical) and positive charge, which were determined by the spin density evaluated by density functional theory (DFT). The structure of M.+ determined by DFT rationally indicated that the compMcLR and compMcLR+1 ions at m/z 224 and 222 are produced by charge migration, while the McLR and McLR+1 ions at m/z 74 and 75 are produced by charge retention. The difference in the peak abundance of m/z 74 and 224 ions were evaluated from the difference in the ionization energy of the corresponding neutral fragments, based on Stevenson's rule.

Fast Heavy-Ion-Induced Anion-Molecule Reactions on the Methanol Droplet Surface.

To gain insight into complex ion-molecule reactions induced by MeV-energy heavy ion irradiation of condensed matter, we performed a mass spectrometric study of secondary ions emitted from methanol microdroplet surfaces by 2.0 MeV C2+. We observed positive and negative secondary ions, including fragments, clusters, and reaction products. We found that a wider variety of negative ions than positive ions (such as C2H-, C2HO-, C2H5O-, and C2H3O2-) were formed. We performed measurements for deuterated methanol (CH3OD) droplets to identify the hydrogen elimination site of the intermediates involved in the reactions and to reveal the mechanism that generates various negative reaction product ions. Comparing the results of CH3OD with CH3OH droplets, we propose that the primary formation mechanism is association reactions of anion and neutral fragments, such as CH3O- + CO → C2H3O2-. Quantum chemical calculations confirmed that the reactions can proceed with no barrier. This study provides new insights into the importance of rapid anion-molecule reactions among fragments as the mechanism that generates complex molecular species in fast heavy-ion-induced reactions.

Integrated Solid-Phase Extraction, Ultra-High-Performance Liquid Chromatography-Quadrupole-Orbitrap High-Resolution Mass Spectrometry, and Multidimensional Data-Mining Techniques to Unravel the Metabolic Network of Dehydrocostus Lactone in Rats.

Dehydrocostus lactone (DL) is among the representative ingredients of traditional Chinese medicine (TCM), with excellent anticancer, antibacterial, and anti-inflammatory activities. In this study, an advanced strategy based on ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was integrated to comprehensively explore the metabolic fate of DL in rats. First, prior to data collection, all biological samples (plasma, urine, and feces) were concentrated and purified using solid-phase extraction (SPE) pre-treatment technology. Then, during data collection, in the full-scan (FS) data-dependent acquisition mode, FS-ddMS2 was intelligently combined with FS-parent ion list (PIL)-dynamic exclusion (DE) means for targeted monitoring and deeper capture of more low-abundance ions of interest. After data acquisition, data-mining techniques such as high-resolution extracted ion chromatograms (HREICs), multiple mass defect filters (MMDFs), diagnostic product ions (DPIs), and neutral loss fragments (NLFs) were incorporated to extensively screen and profile all the metabolites in multiple dimensions. As a result, a total of 71 metabolites of DL (parent drug included) were positively or tentatively identified. The results suggested that DL in vivo mainly underwent hydration, hydroxylation, dihydrodiolation, sulfonation, methylation, dehydrogenation, dehydration, N-acetylcysteine conjugation, cysteine conjugation, glutathione conjugation, glycine conjugation, taurine conjugation, etc. With these inferences, we successfully mapped the "stepwise radiation" metabolic network of DL in rats, where several drug metabolism clusters (DMCs) were discovered. In conclusion, not only did we provide a refined strategy for inhibiting matrix effects and fully screening major-to-trace metabolites, but also give substantial data reference for mechanism investigation, in vivo distribution visualization, and safety evaluation of DL.

Imaging the Dynamics of the Electron Ionization of C2F6

The dissociation of C2F6 following electron ionization at 100 eV has been studied using multimass velocity-map ion imaging and covariance-map imaging analysis. Single ionization events form parent C2F6+ cations in an ensemble of electronic states, which follow a multiplex of relaxation pathways to eventually dissociate into ionic and neutral fragment products. We observe CF3+, CF2+, CF+, C+, F+, C2F5+, C2F4+, C2F2+, and C2F+ ions, all of which can reasonably be formed from singly charged parent ions. Dissociation along the C–C bond typically forms slow-moving, internally excited products, whereas C–F bond cleavage is rapid and impulsive. Dissociation from the à state of the cation preferentially forms C2F5+ and neutral F along a purely repulsive surface. No other electronic state of the ion will form this product pair at the electron energies studied in this work, nor do we observe any crossing onto this surface from higher-lying states of the parent ion. Multiply charged dissociative pathways are also explored, and we note characteristic high kinetic energy release channels due to Coulombic repulsion between charged fragments. The most abundant ion pair we observe is (CF2+, CF+), and we also observe ion pair signals in the covariance maps associated with almost all possible C–C bond cleavage products as well as between F+ and each of CF3+, CF2+, CF+, and C+. No covariance between F+ and C2F5+ is observed, implying that any C2F5+ formed with F+ is unstable and undergoes secondary fragmentation. Dissociation of multiply charged parent ions occurs via a number of mechanisms, details of which are revealed by recoil-frame covariance-map imaging.

Comprehensive Metabolism Study of Tangeretin in Rat Plasma, Urine and Faeces Using Ultra-High Performance Liquid Chromatography-Q Exactive Hybrid Quadrupole- Orbitrap High-Resolution Accurate Mass Spectrometry.

Tangeretin, present in citrus fruits, is a polymethoxy flavone with extensive pharmacological effects. It has been widely used in the clinic, but there were no detailed studies on the in vivo metabolism of tangeretin. This study aimed to establish a rapid and effective strategy to identify the metabolites of tangeretin and evaluate the biotransformation pathways of tangeretin in rats. The ultra-high performance liquid chromatography (UHPLC) equipped with a Q-Exactive Orbitrap mass spectrometer was used to identify the metabolites of tangeretin in plasma, urine and faeces of rats after intragastric administration. Based on high-resolution extracted ion chromatograms (HREICs) and parallel reaction monitoring mode (PRM), metabolites of tangeretin were identified by comparing the accurate mass, chromatographic retention times, diagnostic product ions (DPIs) and neutral loss fragments (NLFs) with those of tangeretin reference standard. Isomers were distinguished by ClogP values. An efficient and integrated strategy was established for the comprehensive screening and characterizing of tangeretin metabolites through Rapid Profiling. Based on this strategy, a total of 52 metabolites were detected and identified, among which 25 metabolites were found in rat plasma, while 48 and 16 metabolites were characterized from rat urine and faeces, respectively. These metabolites were produced by demethylation, demethoxylation, hydroxylation, methoxylation, glucuronidation, glycosylation, sulfation, and their composite reactions. Interestingly, tangeretin is easy to lose methyl in vivo and becomes an intermediate product, and then other phase I and phase II reactions occur. Moreover, the characteristic fragmentation pathways of tangeretin were summarized for the subsequent metabolite identification. The analytical method based on UHPLC-Q-Exactive mass spectrometer has the ability to quickly clarify unknown metabolism. And the the comprehensive metabolism study of tangeretin provided an overall metabolic profile, which will be of great scientific basis for further studies on tangeretin in determining its pharmacokinetics, the bioactivity of the metabolites, and clinical applications.

Comprehensive analysis of dihydromyricetin metabolites in rats using ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry.

As the most abundant and bioactive constituent in vine tea (Ampelopsis grossedentata), dihydromyricetin possesses numerous biological activities. A rapid profiling and identification method for dihydromyricetin metabolites in rats after the oral administration has been established using ultra-high-performance liquid chromatography-Q-Exactive Orbitrap mass spectrometry coupled with multiple data-mining methods. Herein, an efficient analytical strategy characterized by a parallel reaction monitoring mode combining diagnostic fragment ions filtering techniques was developed for the comprehensive identification of dihydromyricetin metabolites in rat plasma, urine, and feces. And then, the biotransformation pathways of dihydromyricetin were further revealed. As a result, a total of 49 metabolites were finally identified by comparing diagnostic fragment ions, chromatographic retention times, neutral loss fragment ions, and accurate mass measurement with those of the dihydromyricetin reference standard. These metabolites were presumed to be dominantly generated through hydroxylation, dehydroxylation, methylation, reduction, sulfation, decarbonylation, glucuronidation, glucosylation, and their composite reactions. In a word, our present results not only supplied a solid foundation to better understand the action mechanism of dihydromyricetin, but also provided some models for the metabolism study of the other compounds in traditional Chinese medicines or natural plants.

Feature MS fragments-based method for identification of toxic furanoids in biological samples

Numerous furan-containing compounds have been reported to be toxic. The toxicity may be attributed to the metabolic activation of the furan ring to cis-enediones. Identification of unknown furans that undergo bioactivation is challenging. Here, we present a novel approach that enables non-targeted profiling of bioactivation of unknown furanoids both in vitro and in vivo. Cyclic pyrrole-glutathione conjugate was the predominant product of cis-enediones with glutathione. The shared glutathione substructure of conjugates was capable of generating four constant and signature fragments under collision-induced dissociation (CID) in the mass spectrometer, including neutral loss fragments 103.0269 Da and 146.0691 Da and product ions at m/z 130.0499 and 177.0328. The unique structure and high abundance of conjugates in combination with the consistency and specificity of CID fragmentation brought extraordinarily high selectivity and reliability for the four fragments as a fingerprint of bioactivated furanoids. The bioactivated furanoids can be identified by screening the four fragments in high-resolution MS/MS datasets using the neutral loss filtering and diagnostic fragmentation filtering of data post-acquisition software MZmine. The simultaneous formation of four individual signal points in the filtering channel with the same precursor ion and retention time was assigned to be furanoids. The method has been rigorously validated. In the pooled urine samples from nine model furanoids-treated mice, nine cis-enediones from the parent furanoids and two from furanoid metabolites were accurately detected and identified. The method showed great performance in non-targeted profiling bioactivated furanoids and their metabolites in urine samples of herbal extract-treated mice.

Charge delocalization error in Piris natural orbital functionals.

Piris Natural Orbital Functionals (PNOFs) have been recognized as a low-scaling alternative to study strong correlated systems. In this work, we address the performance of the fifth functional (PNOF5) and the seventh functional (PNOF7) to deal with another common problem, the charge delocalization error. The effects of this problem can be observed in charged systems of repeated well-separated fragments, where the energy should be the sum of the charged and neutral fragments, regardless of how the charge is distributed. In practice, an energetic overstabilization of fractional charged fragments leads to a preference for having the charge delocalized throughout the system. To establish the performance of PNOFs regarding charge delocalization error, charged chains of helium atoms and the W4-17-MR set molecules were used as base fragments, and their energy, charge distribution, and correlation regime were studied. It was found that PNOF5 prefers localized charge distributions, while PNOF7 improves the treatment of interpair static correlation and tends to the correct energetic limit for several cases, although a preference for delocalized charge distributions may arise in highly strong correlation regimes. Overall, it is concluded that PNOFs can simultaneously deal with static correlation and charge delocalization errors, resulting in a promising choice to study charge-related problems.

Observation of Transient Anions That Do Not Decay through Dissociative Electron Attachment: New Pathways for Radiosensitization.

Low-energy electrons (LEEs) can very efficiently induce bond breaking via dissociative electron attachment (DEA). While DEA is ubiquitous, the importance of other reactions initiated by LEEs remains much more elusive. Here, we looked into this question by measuring highly accurate total cross sections for electron scattering from 1-methyl-5-nitroimidazole (1M5NI), a model radiosensitizer. The small uncertainty and high energy resolution allow us to identify many resonant features related to the formation of transient anions. In addition to novel insights about DEA reactions through the lower-lying resonances, our key finding is that the higher-lying resonances do not undergo DEA, implying alternative decay channels with significant cross sections. In particular, dissociation into two neutral fragments is probably involved in the case of 1M5NI. This finding has direct implications for the understanding of LEE-induced chemistry, particularly in the fundamental processes underlying the radiosensitization activity.

Negative Atmospheric Pressure Chemical Ionization of Chlorinated Hydrocarbons Studied by Ion Mobility Spectrometry (IMS) and IMS-MS Techniques

Negative polarity atmospheric pressure chemical ionization of selected chlorinated hydrocarbons (tetrachloromethane CCl4 and hexachloroethane C2Cl6, dichloromethane CH2Cl2, trichloromethane CHCl3, 1,1,1,2-tetrachloroethane 1,1,1,2-C2H2Cl4, 1,1,2,2-tetrachloroethane 1,1,2,2,-C2H2Cl4 1,1,2-trichloroethane 1,1,2-C2H3Cl3, and 1,1,2-trichloroethane 1,1,2-C2HCl3) was studied using ion mobility spectrometry (IMS) and IMS combined with time-of-flight mass spectrometer (IMS-TOF MS) techniques, in the dry air and at two different drift gas temperatures (323 and 373 K). The ionization was performed using the O2-CO2(H2O)0,1 reactant ions (RIs), and the dominant ionization reaction was the dissociative electron transfer. The ionization resulted in the appearance of Cl- ions for all substances and [O2H..Cl]- ions, which were absent in the case of perchlorinated substances. The quantum-chemical calculations at the density functional theory level of theory using the ωB97X-D/aug-cc-pVTZ method were performed to calculate the thermochemical data (heats of formations, electron affinities, reaction enthalpies) for RIs, neutral substances, neutral fragments, and the anionic fragments. The calculations supported the experimental observations regarding the endothermicity of the Cl- channel for all substances and the exothermicity of the [O2H..Cl]- channel for the tetrachloro- and trichloroethanes.