Resonant Formation of Strand Breaks in Sensitized Oligonucleotides Induced by Low-Energy Electrons (0.5-9 eV)

Many experimental and theoretical advances have recently allowed the study of direct and indirect effects of low-energy electrons (LEEs) on DNA damage. In an effort to explain how LEEs damage the human genome, researchers have focused efforts on LEE interactions with bacterial plasmids, DNA bases, sugar analogs, phosphate groups, and longer DNA moieties. Here, we summarize the current understanding of the fundamental mechanisms involved in LEE-induced damage of DNA and complex biomolecule films. Results obtained by several laboratories on films prepared and analyzed by different methods and irradiated with different electron-beam current densities and fluencies are presented. Despite varied conditions (e.g., film thicknesses and morphologies, intrinsic water content, substrate interactions, and extrinsic atmospheric compositions), comparisons show a striking resemblance in the types of damage produced and their yield functions. The potential of controlling this damage using molecular and nanoparticle targets with high LEE yields in targeted radiation-based cancer therapies is also discussed.

We overview our recent theoretical predictions and the innovative experimental findings that inspired us concerning the mechanisms by which very low-energy (0.1-2 eV) free electrons attach to DNA and cause strong (ca. 4 eV) covalent bonds to break causing so-called single-strand breaks. Our primary conclusions are that (i) attachment of electrons in the above energy range to base pi* orbitals is more likely than attachment elsewhere and (ii) attachment to base pi* orbitals most likely results in cleavage of sugar-phosphate C-O sigma bonds. Later experimental findings that confirmed our predictions about the nature of the electron attachment event and about which bonds break when strand breaks form are also discussed. The proposed mechanism of strand break formation by low-energy electrons involves an interesting through-bond electron-transfer process.