Substitution of the thymidine moiety in DNA by C5-substituted halogenated thymidine analogues causes significant augmentation of radiation damage in living cells. However, the molecular pathway involved in such radiosensitization process has not been clearly elucidated to date in solution at room temperature. So far, low-energy electrons (LEEs; 0–20 eV) under vacuum condition and solvated electrons (esol–) in solution are shown to produce the σ-type C5-centered pyrimidine base radical through dissociative electron attachment involving carbon–halogen bond breakage. Formation of this σ-type radical and its subsequent reactions are proposed to cause cellular radiosensitization. Here, we report time-resolved measurements at room temperature, showing that a radiation-produced quasi-free electron (eqf–) in solution promptly breaks the C5-halogen bond in halopyrimidines forming the σ-type C5 radical via an excited transient anion radical. These results demonstrate the importance of ultrafast reactions of eqf–, which are extremely important in chemistry, physics, and biology, including tumor radiochemotherapy.
by Jun Ma, Anil Kumar, Yusa Muroya, Shinichi Yamashita, Tsuneaki Sakurai, Sergey A. Denisov, Michael D. Sevilla, Amitava Adhikary, Shu Seki and Mehran Mostafavi
Damage to DNA via dissociative electron attachment has been well-studied in both the gas and condensed phases; however, understanding this process in bulk solution at a fundamental level is still a challenge. Here, we use a picosecond pulse of a high energy electron beam to generate electrons in liquid diethylene glycol and observe the electron attachment dynamics to ribothymidine at different stages of electron relaxation. Our transient spectroscopic results reveal that the quasi-free electron with energy near the conduction band effectively attaches to ribothymidine leading to a new absorbing species that is characterized in the UV-visible region. This species exhibits a nearly concentration-independent decay with a time constant of ~350 ps. From time-resolved studies under different conditions, combined with data analysis and theoretical calculations, we assign this intermediate to an excited anion radical that undergoes N1-C1′ glycosidic bond dissociation rather than relaxation to its ground state.
by Jun Ma, Sergey A. Denisov, Jean-Louis Marignier, Pascal Pernot, Amitava Adhikary, Shu Seki and Mehran Mostafavi
The primary localization process of radiation-induced charges (holes (cation radical sites) and excess electrons) remains poorly understood, even at the level of monomeric DNA/RNA models, in particular, in an aqueous environment. We report the first spectroscopic study of charge transfer occurring in radiolysis of aqueous uridine 5′-monophosphate (UMP) solutions and its components: uridine, uracil, ribose, and phosphate. Our results show that prehydrated electrons effectively attach to the base site of UMP; the holes in UMP formed by either direct ionization or reaction of UMP with the radiation-mediated water cation radical (H2O•+) facilely localize on the ribose site, despite the fact that a part of them were initially created on either the phosphate or uracil. The nature of phosphate-to-sugar hole transfer is characterized as a barrierless intramolecular electron transfer with a time constant of 2.5 ns, while the base-to-sugar hole transfer occurs much faster, within a 5 ps electron pulse.
by Furong Wang, Pierre Archirel, Yusa Muroy, Shinichi Yamashita, Pascal Pernot, Chengying Yin, Abdel Karim El Omar, Uli Schmidhammer, Jean-Marie Teuler and Mehran Mostafavi
It is generally considered that the pre-solvated electron and the solvated electron reacting with a solute yield the same product. Silver cyanide complex, Ag(CN)2−, is used as a simple probe to demonstrate unambiguously the existence of a different reduction mechanism for pre-hydrated electrons. Using systematic multichannel transient absorption measurements at different solute concentrations from millimolar to decimolar, global data analysis and theoretical calculations, we present the dissociative electron attachment on Ag(CN)2−. The short-lived silver complex, Ag0(CN)22−, formed by hydrated electron with nanosecond pulse radiolysis, can be observed at room temperature. However, at higher temperatures only the free silver atom, Ag0, is detected, suggesting that Ag0(CN)22− dissociation is fast. Surprisingly, pulse radiolysis measurements on Ag(CN)2− reduction, performed by a 7 ps electron pulse at room temperature, show clearly that a new reduced form of silver complex, AgCN−, is produced within the pulse. This species, absorbing at 560 nm, is not formed by the hydrated electron but exclusively by its precursor. DFT calculations show that the different reactivity of the hydrated and pre-hydrated electrons can be due to the formation of different electronic states of Ag0(CN)22−: the prehydrated electron can form an excited state of this complex, which mainly dissociates into Ag0CN− + CN−.