Selective Excision of C5 from D‐Ribose in the Gas Phase by Low‐Energy Electrons (0–1 eV): Implications for the Mechanism of DNA Damage

Abstract

Sugar is the central unit within a nucleotide connecting the DNA base with the phosphate group, which itself couples to the neighboring nucleotides within single-stranded DNA. The study of the excitation, ionization, and fragmentation of biomolecular systems is essential for the understanding of many problems in the area of life sciences such as the mechanism of radiation damage in cellular systems or the action of radiosensitisers used in tumor therapy.The passage of high-energy radiation through dense media such as water or a living cell leaves a trace of free electrons. These secondary electrons are created in numbers (5 10 4 per MeV of deposited energy [1] ) that makes them the most abundant radiolytic species. In the course of thermalization they can induce further ionization or excitation processes, but they can also efficiently attach at specific energies (resonances) and sites to DNA, forming transient negative ions that subsequently dissociate (dissociative electron attachment, DEA). [2] Ample evidence exists that DEA with its unique features plays an important role in the nascent states of cellular DNA radiolysis.[2] To date, these phenomena have been investigated at two extremes of DNA complexity, namely, plasmid DNA and isolated nucleobases in the gas phase. Experiments on plasmid DNA have demonstrated that low-energy electrons can efficiently induce single-strand breaks (SSBs), as well as double-strand breaks (DSBs).[3] In the very low-energy domain (0-3 eV), below the threshold of electronic excitation, only SSBs are observed. [4] In these experiments it became apparent that the efficiency of both DSBs and SSBs as a function of the primary electron energy exhibits a resonant behavior, indicating that the formation of negativeion resonances is the initial step.Studies on isolate nucleobases (NBs) in the gas phase [5][6][7][8][9][10][11] have demonstrated that they undergo DEA in the range of roughly 6-9 eV and also at much lower energies (< 3 eV) where SSBs are observed.[5] While the high-energy feature leads to loss of H À and further fragment ions associated with the rupture of the NB ring structure, [5][6][7] the low-energy resonance exclusively leads to the loss of neutral hydrogen with the excess charge remaining on the nucleobase.In a recent theoretical study [12] modeling a section of DNA composed of cytosine, sugar, and the phosphate group, an interesting mechanism for electron-initiated strand breaks was proposed. The calculations predict a low-lying anionic potential energy surface that connects the initial p* anion state of the base to a s* state in the backbone. An electron captured by a DNA base may thereby be transferred to the backbone, leading to rupture of the CÀO bond between the phosphate and the sugar. On the other hand, very recent experiments on thymidine (thymine coupled to sugar) [13] indicate that such an electron transfer is not operative; instead it appears that sugar moiety itself has a pronounced ability to capture low-energy electrons with subsequent fragmentation. For t...

Selective Bond Cleavage in Potassium Collisions with Pyrimidine Bases of DNA

“…One can clearly see that there is evidence of neither the parent nor its dehydrogenated anion formation, where the latter was only reported in previous DEA studies. 10,11,13,15 A close inspection of Table I reveals that fragment anions m/z 25, 41, 43, and 45 were not reported in DEA experiments. Regarding the absence of the dehydrogenated parent anion (DR-H) − formation, it is interesting to note that in DEA its resonance profile (shape and energy position) is similar to other fragments.…”

“…Regarding the first, such fragment anions have been also reported in DEA studies. 10,11,13,15 In the case of fructose, it was shown 51 eV). Furthermore, positive ion spectra in electron interactions with D-ribose report the presence of H 2 O + .…”

“…Indeed, as was shown in DEA studies that make a criterion use of isotope-labelled ribose rings, formation of water molecules does not appear to stem from the C 1 -H bond. 10 Regarding the third question, it is known that (DR-H 2 O) − and (DR-2H 2 O) − formations stem from accessing the same initial state. According to DEA experiments, 13 these fragments show near 0 eV resonances reminiscent of dissociation mechanisms present in other molecules, such as the well-explored case of uracil/thymine.…”

“…ciative electron attachment (DEA) processes. 1,[10][11][12][13][14][15][16][17] However, data on the interaction with electron-donating projectiles, i.e., electron transfer processes in potassium-molecule collisions, are, as far as authors are aware, absent. As such, studying the processes that occur in the context of electron transfer in atom-molecule collisions can be a stepping stone in our understanding of some of the molecular mechanisms that can happen in non-gas-phase environments.…”

“…10 The water abstraction sites were explored in more detail in this study, and a tentative identification of some sequential reaction channels was performed. 10 Another interesting study using a Fourier transform ion cyclotron resonance mass spectrometer and density functional theory (DFT) calculations 29 concluded that, upon heating in the gas-phase D-ribose, the molecule changes its geometry to form a pyranose structure (six-membered ring) rather than keeping its furanose form (five-membered ring), the latter present in the DNA/RNA framework. 29 As such, this study concludes that the dominant conformer in gas-phase D-ribose is the pyranose form.…”