Electron-Induced Damage Mechanisms in Biomolecular Systems

Electron-induced damage in biomolecules arises when free or quasi-free electrons interact with molecular targets, leading to a cascade of events that compromise structural integrity and biological function. Such electrons are generated as primary radiation products or secondary species via water radiolysis and can range in energy from fully solvated electrons to low-energy electrons (LEEs) below 20 eV. Direct interactions involve electron attachment to molecular orbitals, triggering bond cleavages through processes such as dissociative electron attachment (DEA) and electron-induced proton transfer (EIPT). Indirect damage pathways stem from reactive intermediates formed upon electron capture, including radical anions and electron-driven fragmentation products. The efficiency and outcome of these interactions depend critically on the local environment: solvent cage effects, hydration shells, hydrogen bonding networks and molecular topology modulate both the energy redistribution and the fate of transient negative ions. Understanding these multiscale mechanisms, from quantum coherence emerging in electron scattering to the macroscopic preservation of biological specimens, is vital for optimizing radiotherapy, improving structural biology methods and elucidating prebiotic chemical evolution.

Research from Nature Portfolio

Recent studies have extended our comprehension of how non-resonant inelastic electron scattering can induce coherent dynamics in simple molecular systems, revealing that generic electron collisions transfer multiple quanta of angular momentum and may trigger asymmetric bond rearrangement. Investigations into prebiotic chemistry demonstrate that very low-energy electrons, in conjunction with ultraviolet radiation, selectively destabilise non-complementary nucleobases, implying that complementary base pairs possess an intrinsic resilience to combined electronic and photonic assault. Seminal work on a clinical radiosensitiser highlights that low-energy electrons can efficiently reduce pro-drug molecules via associative electron attachment, thereby activating cytotoxic species within hypoxic tumour microenvironments while sparing healthy tissue through hydration-mediated suppression of dissociative channels.

Electron-Induced Damage Mechanisms in Biomolecular Systems publication trend

The graph below shows the total number of articles in electron-induced damage mechanisms in biomolecular systems across all publications each year (not limited to Nature Index journals).

Technical terms

Low-energy electrons (LEEs): Electrons with kinetic energies below ~20 eV, produced by ionising radiation and capable of inducing bond-specific damage in biomolecules.

Dissociative electron attachment (DEA): A process whereby an electron transiently binds to a molecule, forming a negative ion that dissociates to yield fragment ions and neutral fragments.

Electron-induced proton transfer (EIPT): Intramolecular proton relocation within a transient anion that can stabilise the negative charge and inhibit bond cleavage.

Associative electron attachment: A non-dissociative capture of an electron by a molecule, leading to a stable radical anion without immediate bond rupture.

Cage effect: The confinement of dissociation fragments by surrounding solvent or matrix molecules, limiting their spatial separation and further reaction.

References

1. Unraveling the Complexity of DNA Radiation Damage Using DNA Nanotechnology. Accounts of Chemical Research (2024).
2. Inelastic electron scattering induced quantum coherence in molecular dynamics. Nature Communications (2023).
3. Intramolecular Proton Transfer in the Radical Anion of Cytidine Monophosphate Sheds Light on the Sensitivities of Dry vs Wet DNA to Electron Attachment-Induced Damage. Journal of the American Chemical Society (2023).
4. The cage effect of electron beam irradiation damage in cryo-electron microscopy. npj Computational Materials (2024).
5. Prebiotic chemical origin of biomolecular complementarity. Communications Chemistry (2023).
6. Low-energy electrons transform the nimorazole molecule into a radiosensitiser. Nature Communications (2019).