No 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...

Leaner, meaner cisplatin: Dissociative electron attachment to the anticancer drug cisplatin (1) shows intense resonances at very low energies, which result in PtCl bond cleavage. A single low‐energy electron can trigger the loss of both chlorine atoms from cisplatin (see scheme), thereby forming [Pt(NH3)2]−. This complex is the reactive intermediate to form cisplatin–DNA adducts, which consequently inhibit DNA replication.

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.

We use dibutyl phosphate to simulate the behavior of the phosphate group in DNA towards the attack of low energy electrons. We find that the compound undergoes effective dissociative electron attachment within a low energy resonant feature at 1 eV and a further resonance peaking at 8 eV. The dissociative electron attachment (DEA) reactions are associated with the direct cleavage of the C-O and the P-O bond but also the excision of the PO-, PO3-, H2PO3- units. For the phosphate group coupled in the DNA network these reactions represent single strand breaks. We hence propose that the most direct mechanism of single strand breaks occurring in DNA at subexcitation energies (< 4 eV) is due to DEA directly to the phosphate group.