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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Temperature dependence of the cross section for the fragmentation of thymine via dissociative electron attachment.

Providing experimental values for absolute Dissociative Electron Attachment (DEA) cross sections for nucleobases at realistic biological conditions is a considerable challenge. In this work, we provide the temperature dependence of the cross section, σ, of the dehydrogenated thymine anion (T - H)(-) produced via DEA. Within the 393-443 K temperature range, it is observed that σ varies by one order of magnitude. By extrapolating to a temperature of 313 K, the relative DEA cross section for the production of the dehydrogenated thymine anion at an incident energy of 1 eV decreases by 2 orders of magnitude and the absolute value reaches approximately 6 × 10(-19) cm(2). These quantitative measurements provide a benchmark for theoretical prediction and also a contribution to a more accurate description of the effects of ionizing radiation on molecular medium.

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.

Low energy electron attachment to the nucleotide deoxycytidine monophosphate: direct evidence for the molecular mechanisms of electron-induced DNA strand breaks.

Reactions induced by the attachment of low energy electrons to an entire gas phase nucleotide (2'-deoxycytidine 5'-monophosphate) are reported for the first time. From the resonant attachment profiles information on the site of initial electron localization and from the observed ionic fragments information on final bond cleavage can be extracted.

Decomposition of methionine by low energy electrons.

In this work, we present the results from low energy (<12 eV) electron impact on isolated methionine, Met. We show that dissociative electron attachment is the operative mechanism for the sulfur content amino-acid fragmentation. The two most dominant fragments are attributed to the (Met-H)(-) and (C(4)NOH(5))(-) ions that are formed at energy below 2 eV. The formation of the latter anion is accompanied by the loss of neutral counterparts, which are most likely a water molecule and highly toxic methanethiol, CH(3)SH. Further fragments are associated with the damage at the sulfur end of the amino acid, producing the methyl sulfide anion CH(3)S(-) or sulfur containing neutrals. In the context of radiation induced damage to biological material at the nano-scale level, the present interest of methionine arises from the implication of the molecule in biological processes (e.g., S-adenosyl methionine for the stimulation of DNA methyltransferase reactions or protein synthesis).

Low energy (0-10 eV) electron driven reactions in the halogenated organic acids CCl3COOH, CClF2COOH, and CF3CHNH2COOH (trifluoroalanine).

Negative ion formation following resonant electron attachment to the three title molecules is studied by means of a beam experiment with mass spectrometric detection of the anions. All three molecules exhibit a pronounced resonance in the energy range around 1 eV which decomposes by the loss of a neutral hydrogen atom thereby generating the closed shell anion (M-H)(-) (or RCOO(-)), a reaction which is also a common feature in the non-substituted organic acids. The two chlorine containing molecules CCl(3)COOH and CClF(2)COOH exhibit an additional strong and narrow resonance at very low energy (close to 0 eV) which decomposes by the cleavage of the C-Cl bond with the excess charge finally localised on either of the two fragments Cl(-) and (M-Cl)(-). This reaction is by two to three orders of magnitude more effective than hydrogen loss. Apart from these direct bond cleavages (C-Cl, O-H) resonant attachment of subexcitation electrons trigger additional remarkably complex unimolecular decompositions leading, e.g., to the formation of the bihalide ions ClHCl(-) and ClHF(-) from CCl(3)COOH and CClF(2)COOH, respectively, or the loss of a neutral CF(2) unit from trifluoroalanine thereby generating the fluoroglycine radical anion. These reactions require substantial rearrangement in the transitory negative ion, i.e., the cleavage of different bonds and formation of new bonds. F(-) from both chlorodifluoroacetic acid and trifluoroalanine is formed at comparatively low intensity (more than three orders of magnitude less than Cl(-) from the chlorine containing molecules) and predominantly within a broad resonant feature around 7-8 eV characterised as core excited resonance.