Direct observation of ultrafast-electron-transfer reactions unravels high effectiveness of reductive DNA damage

Abstract

Both water and electron-transfer reactions play important roles in chemistry, physics, biology, and the environment. Oxidative DNA damage is a well-known mechanism, whereas the relative role of reductive DNA damage is unknown. The prehydrated electron (e(pre)-), a novel species of electrons in water, is a fascinating species due to its fundamental importance in chemistry, biology, and the environment. e(pre)- is an ideal agent to observe reductive DNA damage. Here, we report both the first in situ femtosecond time-resolved laser spectroscopy measurements of ultrafast-electron-transfer (UET) reactions of e(pre)- with various scavengers (KNO(3), isopropanol, and dimethyl sulfoxide) and the first gel electrophoresis measurements of DNA strand breaks induced by e(pre)- and OH(•) radicals co-produced by two-UV-photon photolysis of water. We strikingly found that the yield of reductive DNA strand breaks induced by each e(pre)- is twice the yield of oxidative DNA strand breaks induced by each OH(•) radical. Our results not only unravel the long-standing mystery about the relative role of radicals in inducing DNA damage under ionizing radiation, but also challenge the conventional notion that oxidative damage is the main pathway for DNA damage. The results also show the potential of femtomedicine as a new transdisciplinary frontier and the broad significance of UET reactions of e(pre)- in many processes in chemistry, physics, biology, and the environment.

Electron transfer-based combination therapy of cisplatin with tetramethyl- p -phenylenediamine for ovarian, cervical, and lung cancers

“…The high reactivity of cisplatin with electrons has been confirmed subsequently by Kopyra et al (33) in studying dissociative attachments of low-energy free electrons to gas-phase CDDP. It is well known that in liquid water, free electrons produced by ionizing radiation will rapidly become e pre − on the fs timescale and finally form the nonreactive solvated electrons (6,7,9). Most recently, quantum chemical calculations by Kuduk-Jaworska et al (34) have confirmed the DET mechanism of CDDP.…”

“…biophysics | physical biology | chemical biology | biological chemistry E lectron-transfer reactions play key roles in diverse processes in chemistry, physics, and biology, ranging from photo-induced reactions (1,2), electron tunneling in proteins (3), and electron transport in DNA (4) to the ozone hole formation (5) and reductive DNA damage (6,7). Electron-transfer reactions in molecular systems have therefore been the subject of intense experimental and theoretical studies.…”

Communication: Electronic UV-Vis transient spectra of the ·OH reaction products of uracil, thymine, cytosine, and 5,6-dihydrouracil by using the complete active space self-consistent field second-order perturbation (CASPT2//CASSCF) theory

“…DNA/RNA oxidation by · OH radical remains a field of active research. [25][26][27][28][29] Therefore, accurate determinations of the spectroscopic features of the radical products are relevant to unambiguously recognize such species in the experiments.…”

Understanding the Interaction between Low-Energy Electrons and DNA Nucleotides in Aqueous Solution

“…Sanche et al, 8,9 have demonstrated that electrons with energies as low as 0 eV can cause strand breaks in dry DNA. Nguyen et al 10 have shown that the low energy electrons produced following the radiolysis of water, cause the most damage to aqueous DNA. In particular, their results suggest that reductive damage caused by low energy electrons lead to more strand breaks than oxidative damage caused by OH · radicals.…”