Fragmentation of 5-fluorouridine induced by low energy (< 12 eV) electrons: insights into the radiosensitization of DNA.

5-Fluorouracil is now routinely used in chemo- and radiotherapy. Incorporated within DNA, the molecule is bound to the sugar backbone, forming the 5-fluorouridine sub-unit investigated in the present work. For the clinical usage of the latter, no information exists on the mechanisms that control the radiosensitizing effect at the molecular level. As low energy (< 12 eV) electrons are abundantly produced along the radiation tracks during cancer treatment using beams of high energy particles, we study how these ballistic secondary electrons damage the sensitizing molecule. The salient result from our study shows that the N-glycosidic bonds are principally affected with a cross-section of approximately two orders of magnitude higher than the canonical thymidine, reflecting to some degree the surviving factor of radiation-treated carcinoma cells with and without 5-fluorouracil incorporation. This result may help in the comprehension of the radiosensitizing effect of the fluoro-substituted thymidine in DNA.

Fragmentation of metal(II) bis(acetylacetonate) complexes induced by slow electrons.

Nowadays, organometallic complexes receive particular attention because of their use in the design of pure nanoscale metal structures. In the present work, we present results obtained from a series of studies on the degradation of metal(II) bis(acetylacetonate)s induced by low-energy electrons. These slow particles induce the formation of the acetylacetonate anion, [acac]-, and the parent anion as the most dominant species at incident electron energies near 0 eV. They also fragment the organometallic compounds via various competitive reaction channels that occur at higher energies via dissociative electron attachment. The reported data may contribute to a better understanding of the physical chemistry underlying the electron-molecule interactions, which is crucial for potential applications of these molecular systems in the deposition of nanoscale structures.

Fragmentation of the DNA Lesion 8-oxo-Guanine by Low-Energy Electrons.

8-oxo-Guanine is a mutagenic lesion produced by reactions involving reactive oxygen species and guanine in DNA. Its production induces mispairing between the canonical nucleobases during DNA replication such that various types of cancers are associated with the DNA lesion. Since radiation therapy is used in some cases, the interaction of low-energy electrons with 8-oxo-guanine can in turn produce other reactive species, which in principle could have either a detrimental or protective effect on the organism. Motivated by these facts, we report a comparative experimental study of electron-induced fragmentation of guanine and 8-oxo-guanine, along with a theoretical study of the π* shape resonances and bound anion states, which may trigger those dissociation reactions. The electron-induced fragmentation of 8-oxo-guanine is remarkably distinct from the native form. More complex reactions were observed for the oxidized species, which may produce several anion fragments at very low energies (∼0 eV). The dehydrogenated parent anion, which is already a minor fragment in guanine, was completely suppressed in 8-oxo-guanine. The calculated thermodynamical thresholds also suggest that NH2 elimination in guanine, at sub-excitation energies, proceeds via a complex reaction involving rearrangement steps.

Controlling the diversity of ion-induced fragmentation pathways by N-methylation of amino acids.

We present a combined experimental and theoretical study of the fragmentation of singly and doubly N-methylated glycine (sarcosine and N,N-dimethyl glycine, respectively) induced by low-energy (keV) O6+ ions. Multicoincidence mass spectrometry techniques and quantum chemistry simulations (ab initio molecular dynamics and density functional theory) allow us to characterise different fragmentation pathways as well as the associated mechanisms. We focus on the fragmentation of doubly ionised species, for which coincidence measurements provide unambiguous information on the origin of the various charged fragments. We have found that single N-methylation leads to a larger variety of fragmentation channels than in no methylation of glycine, while double N-methylation effectively closes many of these fragmentation channels, including some of those appearing in pristine glycine. Importantly, the closure of fragmentation channels in the latter case does not imply a protective effect by the methyl group.

Timing of charge migration in betaine by impact of fast atomic ions.

The way molecules break after ion bombardment is intimately related to the early electron dynamics generated in the system, in particular, charge (or electron) migration. We exploit the natural positive-negative charge splitting in the zwitterionic molecule betaine to selectively induce double electron removal from its negatively charged side by impact of fast O6+ ions. The loss of two electrons in this localized region of the molecular skeleton triggers a competition between direct Coulomb explosion and charge migration that is examined to obtain temporal information from ion-ion coincident measurements and nonadiabatic molecular dynamics calculations. We find a charge migration time, from one end of the molecule to the other, of approximately 20 to 40 femtoseconds. This migration time is longer than that observed in molecules irradiated by ultrashort light pulses and is the consequence of charge migration being driven by adiabatic nuclear dynamics in the ground state of the molecular dication.

Experimental and Theoretical Studies of Dissociative Electron Attachment to Metabolites Oxaloacetic and Citric Acids.

In this contribution the dissociative electron attachment to metabolites found in aerobic organisms, namely oxaloacetic and citric acids, was studied both experimentally by means of a crossed-beam setup and theoretically through density functional theory calculations. Prominent negative ion resonances from both compounds are observed peaking below 0.5 eV resulting in intense formation of fragment anions associated with a decomposition of the carboxyl groups. In addition, resonances at higher energies (3-9 eV) are observed exclusively from the decomposition of the oxaloacetic acid. These fragments are generated with considerably smaller intensities. The striking findings of our calculations indicate the different mechanism by which the near 0 eV electron is trapped by the precursor molecule to form the transitory negative ion prior to dissociation. For the oxaloacetic acid, the transitory anion arises from the capture of the electron directly into some valence states, while, for the citric acid, dipole- or multipole-bound states mediate the transition into the valence states. What is also of high importance is that both compounds while undergoing DEA reactions generate highly reactive neutral species that can lead to severe cell damage in a biological environment.

Fragmentation of Nickel(II) and Cobalt(II) Bis(acetylacetonate) Complexes Induced by Slow (<10 eV) Electrons.

Metal acetylacetonate complexes have high potentiality in nanoscale fabrication processes (e.g., focus electron beam-induced deposition) thanks to the versatile character and ease of preparation compounds. In this work, we study and compare the physics and the physicochemistry induced by the interaction of low-energy (<10 eV) electrons with nickel(II) and cobalt(II) bis(acetylacetonate) complexes. The slow particles decompose the molecules via dissociative electron attachment. The nickel(II) and cobalt(II) bis(acetylacetonate) anions and the acetylacetonate negative fragments are the most dominant detected species. The experimental data are completed with density functional theory calculations to provide information on the electronic states of the molecules and the energetics for fragmentation. Finally, it is found that the interaction of low-energy electrons resulting in the decomposition of organometallic complexes in the gas phase is more efficient with the nickel(II) than with the cobalt(II) bis(acetylacetonate) complex. These results are found to be in a relative agreement with the surface experiments.

Energy-Selective Decomposition of Organometallic Compounds by Slow Electrons: The Case of Chloro(dimethyl sulfide)gold(I).

Gold-containing compounds offer many applications in nanoscale materials science, and electron-beam methods are versatile for shaping nanostructures. In this study, we report the energy-selective fragmentation of chloro(dimethyl sulfide)gold(I) (ClAuS(CH3)2) induced by slow electrons. We observe the resonant formation of four fragment anions, namely [Cl]-, [S]-, [CH2S]-, and [ClAuH···SH]-, which are generated in the energy range of 0-9 eV. The predominant fragment anion is formed below 1 eV from the cleavage of a single Au-Cl bond to produce the [Cl]- anion. The resonant states and the energetics of the fragmentation are investigated by DFT methods. These findings may contribute to future strategies in the elaboration of specific nanomaterials or for selective chemistry using electron-beam techniques.

Decomposition of Bis(acetylacetonate)zinc(II) by Slow Electrons.

The production of zinc-containing nanostructures has a large variety of applications. Using electron beam techniques to degrade organometallic molecules for that purpose is perhaps one of the most versatile methods. In this work, we investigate the scattering of low-energy (<12 eV) electrons with bis(acetylacetonate)zinc(II) molecules. We show that core excited and high-lying shape resonances are mainly responsible for the production of the precursor anions as well as the ligand negative fragments, which are observed exclusively at electron energies of >3 eV. The mechanisms for electron capture and then molecular dissociation are discussed in terms of density functional theory studies.

Interaction of Slow Electrons with Thermally Evaporated Manganese(II) Acetylacetonate Complexes.

Complexes of metal acetylacetonate are used as general precursors for the synthesis of metal oxide nanomaterials. In the present work, we study the interaction of low-energy (<10 eV) electrons, produced abundantly as secondary electrons during the bombardment of the substrate by the primary particles, with thermally evaporated manganese(II) acetylacetonate complexes. We found that the acetylacetonate anion ([acac]-) is the major anionic species produced, while the second most abundant is the parent anion [Mn(II)(acac)2]-. This observation differs from those reported from electron attachment to Cu(acac)2, for which [Cu(II)(acac)2]- is the predominant anion [Kopyra et al. Phys. Chem. Chem. Phys. 2018, 20, 7746]. The experimental data are supported by theory to provide information on the physical-chemistry processes initiated by slow electrons to the organometallic precursor and to interpret the different behavior of Mn(acac)2 compared to Cu(acac)2.

Electron-Induced Reactions in 3-Bromopyruvic Acid.

3-Bromopyruvic acid (3BP) is a potential anti-cancer drug, the action of which on cellular metabolism is not yet entirely clear. The presence of a bromine atom suggests that it is also reactive towards low-energy electrons, which are produced in large quantities during tumour radiation therapy. Detailed knowledge of the interaction of 3BP with secondary electrons is a prerequisite to gain a complete picture of the effects of 3BP in different forms of cancer therapy. Herein, dissociative electron attachment (DEA) to 3BP in the gas phase has been studied both experimentally by using a crossed-beam setup and theoretically through scattering and quantum chemical calculations. These results are complemented by a vacuum ultraviolet absorption spectrum. The main fragmentation channel is the formation of Br- close to 0 eV and within several resonant features at 1.9 and 3-8 eV. At low electron energies, Br- formation proceeds through σ* and π* shape resonances, and at higher energies through core-excited resonances. It is found that the electron-capture cross-section is clearly increased compared with that of non-brominated pyruvic acid, but, at the same time, fragmentation reactions through DEA are significantly altered as well. The 3BP transient negative ion is subject to a lower number of fragmentation reactions than those of pyruvic acid, which indicates that 3BP could indeed act by modifying the electron-transport chains within oxidative phosphorylation. It could also act as a radio-sensitiser.

Ion mobility spectrometers and electron capture detector - A comparison of detection capabilities.

Electron capture detectors (ECDs) and detectors used in ion mobility spectrometry (IMS) have been successfully used for the detection of numerous compounds including hazardous substances. The general principles of their operations are similar and based on sample component ionization and measurement of the signal using the differences in the mobility of electric charge carriers. Differences in sensitivity result from various parameters of these instruments. Value of electric field intensity in ionic reactors have an influence on ionization process. The main goal of the performed tests was to compare the analytical properties of ECD and two types of IMS detectors: a drift tube spectrometer (DT IMS) and a differential mobility spectrometer (DMS). In the work performed, the efficiency of ionization and the response of detectors to selected analytes were compared. ECD, DT IMS and DMS were equipped with 63-Ni radioactive sources. Analytes have been ionized via electron capture process or dissociative electron transfer. Results obtained for oxygen and chloro-substituted organic compounds (carbon tetrachloride, benzyl chloride, chloroform, 2-chloroethyl ethyl sulfide) were used to calculate the relative signal and to compare the ionization efficiency for three detectors. The phenomena observed experimentally were related to energy dependencies and electron capture cross-sections of analytes. The efficiency of ionization in DT IMS was also compared for electron capture when nitrogen was used as the carrier gas, and when the ionization process was based on the collisions of the analyte molecules with the O2- with the use of air.

Insights into the dehydrogenation of 2-thiouracil induced by slow electrons: Comparison of 2-thiouracil and 1-methyl-2-thiouracil.

In the present contribution, we study dissociative electron attachment to 1-methyl-2-thiouracil that has been synthesized and purified prior to the measurements. We compare the results with those previously obtained from 2-thiouracil. The comparison of the yield of the dehydrogenated parent anion from both the compounds allows us to assign the site from which the H atom is expulsed and to predict the mechanism that is involved in the formation of the peaks within the ion yield curve. It appears that the dehydrogenation observed for 2-thiouracil arising from the vibrational Feshbach resonances (at 0.7 and 1.0 eV) and a π*/σ* transition (at 0.1 eV) involves the bond cleavage at the N1 site, while that at the N3 site operates via the π*/σ* transition and occurs in the energy range of 1.1-3.3 eV. Besides the loss of the H atom from 1-methyl-2-thiouracil, we observe a relatively strong signal due to the loss of an entire methyl group (not observed from methyl-substituted thymine and uracil) that is formed from the N1-CH3 bond cleavage and can mimic the N-glycosidic bond cleavage within the DNA macromolecule.

Interaction of gas phase copper(ii) acetylacetonate with slow electrons.

Understanding the fundamental processes underlying the interaction of organometallic compounds with low energy electrons is desirable for optimizing methodologies for nanoscale applications. In this work, we couple experimental measurements with theories to investigate the interaction of gas phase copper(ii) acetylacetonate, Cu(acac)2, with low energy (<12 eV) electrons. Near 0 eV, a multipole-bound anion is likely to act as the doorway for the formation of a transitory molecular anion which then undergoes stabilization via a 90°-rotation of one of the acac units. The production of the parent anion competes with the dissociation processes, generating preferentially the acetylacetonate negative ion. Moreover, at incident electron energies above 3.5 eV, the electron driven fragmentation of Cu(acac)2 is likely to produce atomic Cu. These results can suggest some potential strategies for the deposition of pure copper using an appropriate electron irradiation technique.

Electron-driven and thermal chemistry during water-assisted purification of platinum nanomaterials generated by electron beam induced deposition.

Focused electron beam induced deposition (FEBID) is a versatile tool for the direct-write fabrication of nanostructures on surfaces. However, FEBID nanostructures are usually highly contaminated by carbon originating from the precursor used in the process. Recently, it was shown that platinum nanostructures produced by FEBID can be efficiently purified by electron irradiation in the presence of water. If such processes can be transferred to FEBID deposits produced from other carbon-containing precursors, a new general approach to the generation of pure metallic nanostructures could be implemented. Therefore this study aims to understand the chemical reactions that are fundamental to the water-assisted purification of platinum FEBID deposits generated from trimethyl(methylcyclopentadienyl)platinum(IV) (MeCpPtMe3). The experiments performed under ultrahigh vacuum conditions apply a combination of different desorption experiments coupled with mass spectrometry to analyse reaction products. Electron-stimulated desorption monitors species that leave the surface during electron exposure while post-irradiation thermal desorption spectrometry reveals products that evolve during subsequent thermal treatment. In addition, desorption of volatile products was also observed when a deposit produced by electron exposure was subsequently brought into contact with water. The results distinguish between contributions of thermal chemistry, direct chemistry between water and the deposit, and electron-induced reactions that all contribute to the purification process. We discuss reaction kinetics for the main volatile products CO and CH4 to obtain mechanistic information. The results provide novel insights into the chemistry that occurs during purification of FEBID nanostructures with implications also for the stability of the carbonaceous matrix of nanogranular FEBID materials under humid conditions.

Dissociative electron attachment to coordination complexes of chromium: chromium(0) hexacarbonyl and benzene-chromium(0) tricarbonyl.

Here we report the results of dissociative electron attachment (DEA) to gas-phase chromium(0) hexacarbonyl (Cr(CO)6) and benzene-chromium(0) tricarbonyl ((η6-C6H6)Cr(CO)3) in the energy range of 0-12 eV. Measurements have been performed utilizing an electron-molecular crossed beam setup. It was found that DEA to Cr(CO)6 results (under the given experimental conditions) in the formation of three fragment anions, namely [Cr(CO)5]-, [Cr(CO)4]-, and [Cr(CO)3]-. The predominant reaction channel is the formation of [Cr(CO)5]- due to the loss of one CO ligand from the transient negative ion. The [Cr(CO)5]- channel is visible via two overlapping resonant structures appearing in the energy range below 1.5 eV with a dominant structure peaking at around 0 eV. The peak maxima of the fragments generated by the loss of two or three CO ligands are blue-shifted and the most intense peaks within the ion yield curves appear at 1.4 eV and 4.7 eV, respectively. (η6-C6H6)Cr(CO)3 shows a very rich fragmentation pattern with decomposition leading to the formation of seven fragment anions. Three of them are generated from the cleavage of one, two or three CO ligand(s). The energy of the peak maxima of the [(C6H6)Cr(CO)2]-, [(C6H6)Cr(CO)]-, and [(C6H6)Cr]- fragments is shifted towards higher energy with respect to the position of the respective fragments generated from Cr(CO)6. This phenomenon is most likely caused by the fact that chromium-carbonyl bonds are stronger in the heteroleptic complex (η6-C6H6)Cr(CO)3 than in homoleptic Cr(CO)6. Besides, we have observed the formation of anions due to the loss of C6H6 and one or more CO units. Finally, we found that Cr-, when stripped of all ligands, is generated through a high-energy resonance, peaking at 8 eV.

Temperature Dependence of the Dissociative Electron Attachment to 2-Thiothymine.

We report the temperature dependence for the dissociation of 2-thiothymine induced by low energy electrons. Although hot molecules favor dissociative electron attachment (DEA) initiated by shape/core-excited resonances, here we demonstrate that, in contrast, the dipole bound mediated DEA is inhibited, by decreasing the accessibility for the excess electron to the dipole bound anion formation channel. In addition, from this research the estimation of the change in the cross sections for the fragments production via the shape/core-excited resonances can be extended to temperatures at biological relevance.

Sensitizing DNA Towards Low-Energy Electrons with 2-Fluoroadenine.

2-Fluoroadenine ((2F) A) is a therapeutic agent, which is suggested for application in cancer radiotherapy. The molecular mechanism of DNA radiation damage can be ascribed to a significant extent to the action of low-energy (<20 eV) electrons (LEEs), which damage DNA by dissociative electron attachment. LEE induced reactions in (2F) A are characterized both isolated in the gas phase and in the condensed phase when it is incorporated into DNA. Information about negative ion resonances and anion-mediated fragmentation reactions is combined with an absolute quantification of DNA strand breaks in (2F) A-containing oligonucleotides upon irradiation with LEEs. The incorporation of (2F) A into DNA results in an enhanced strand breakage. The strand-break cross sections are clearly energy dependent, whereas the strand-break enhancements by (2F) A at 5.5, 10, and 15 eV are very similar. Thus, (2F) A can be considered an effective radiosensitizer operative at a wide range of electron energies.

Unusual temperature dependence of the dissociative electron attachment cross section of 2-thiouracil.

At low energies (<3 eV), molecular dissociation is controlled by dissociative electron attachment for which the initial step, i.e., the formation of the transient negative ion, can be initiated by shape resonance or vibrational Feshbach resonance (VFR) mediated by the formation of a dipole bound anion. The temperature dependence for shape-resonances is well established; however, no experimental information is available yet on the second mechanism. Here, we show that the dissociation cross section for VFRs mediated by the formation of a dipole bound anion decreases as a function of a temperature. The change remains, however, relatively small in the temperature range of 370-440 K but it might be more pronounced at the extended temperature range.

N-Acetylglycine Cation Tautomerization Enabled by the Peptide Bond.

We present a combined experimental and theoretical study of the ionization of N-acetylglycine molecules by 48 keV O(6+) ions. We focus on the single ionization channel of this interaction. In addition to the prompt fragmentation of the N-acetylglycine cation, we also observe the formation of metastable parent ions with lifetimes in the microsecond range. On the basis of density functional theory calculations, we assign these metastable ions to the diol tautomer of N-acetylglycine. In comparison with the simple amino acids, the tautomerization rate is higher because of the presence of the peptide bond. The study of a simple biologically relevant molecule containing a peptide bond allows us to demonstrate how increasing the complexity of the structure influences the behavior of the ionized molecule.