Exploring Water Radiolysis in Proton Cancer Therapy: Time-Dependent, Non-Adiabatic Simulations of H\u3csup\u3e+\u3c/sup\u3e + (H2O)1-6

© 2017 Privett et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. To elucidate microscopic details of proton cancer therapy (PCT), we apply the simplest-level electron nuclear dynamics (SLEND) method to H+ + (H2O)1-6 at ELab = 100 keV. These systems are computationally tractable prototypes to simulate water radiolysis reactions - i.e. the PCT processes that generate the DNA-damaging species against cancerous cells. To capture incipient bulk-water effects, ten (H2O)1-6 isomers are considered, ranging from quasi-planar/ multiplanar (H2O)1-6 to smallest-drop prism and cage (H2O)6 structures. SLEND is a time-dependent, variational, non-adiabatic and direct method that adopts a nuclear classicalmechanics description and an electronic single-determinantal wavefunction in the Thouless representation. Short-time SLEND/6-31G∗ (n = 1-6) and /6-31G∗ ∗ (n = 1-5) simulations render cluster-to-projectile 1-electron-transfer (1-ET) total integral cross sections (ICSs) and 1- ET probabilities. In absolute quantitative terms, SLEND/6-31G∗ 1-ET ICS compares satisfactorily with alternative experimental and theoretical results only available for n = 1 and exhibits almost the same accuracy of the best alternative theoretical result. SLEND/6-31G∗ ∗ overestimates 1-ET ICS for n = 1, but a comparable overestimation is also observed with another theoretical method. An investigation on H+ + H indicates that electron direct ionization (DI) becomes significant with the large virtual-space quasi-continuum in large basis sets; thus, SLEND/6-31G∗ 1-ET ICS is overestimated by DI contributions. The solution to this problem is discussed. In relative quantitative terms, both SLEND/6-31∗ and /6-31G∗ ∗ 1-ET ICSs precisely fit into physically justified scaling formulae as a function of the cluster size; this indicates SLEND\u27s suitability for predicting properties of water clusters with varying size. Longtime SLEND/6-31G∗ (n = 1-4) simulations predict the formation of the DNA-damaging radicals H, OH, O and H3O. While smallest-drop isomers are included, no early manifestations of bulk water PCT properties are observed and simulations with larger water clusters will be needed to capture those effects. This study is the largest SLEND investigation on water radiolysis to date

Exploring water radiolysis in proton cancer therapy: Time-dependent, non-adiabatic simulations of H+ + (H2O)1-6.

To elucidate microscopic details of proton cancer therapy (PCT), we apply the simplest-level electron nuclear dynamics (SLEND) method to H+ + (H2O)1-6 at ELab = 100 keV. These systems are computationally tractable prototypes to simulate water radiolysis reactions-i.e. the PCT processes that generate the DNA-damaging species against cancerous cells. To capture incipient bulk-water effects, ten (H2O)1-6 isomers are considered, ranging from quasi-planar/multiplanar (H2O)1-6 to "smallest-drop" prism and cage (H2O)6 structures. SLEND is a time-dependent, variational, non-adiabatic and direct method that adopts a nuclear classical-mechanics description and an electronic single-determinantal wavefunction in the Thouless representation. Short-time SLEND/6-31G* (n = 1-6) and /6-31G** (n = 1-5) simulations render cluster-to-projectile 1-electron-transfer (1-ET) total integral cross sections (ICSs) and 1-ET probabilities. In absolute quantitative terms, SLEND/6-31G* 1-ET ICS compares satisfactorily with alternative experimental and theoretical results only available for n = 1 and exhibits almost the same accuracy of the best alternative theoretical result. SLEND/6-31G** overestimates 1-ET ICS for n = 1, but a comparable overestimation is also observed with another theoretical method. An investigation on H+ + H indicates that electron direct ionization (DI) becomes significant with the large virtual-space quasi-continuum in large basis sets; thus, SLEND/6-31G** 1-ET ICS is overestimated by DI contributions. The solution to this problem is discussed. In relative quantitative terms, both SLEND/6-31* and /6-31G** 1-ET ICSs precisely fit into physically justified scaling formulae as a function of the cluster size; this indicates SLEND's suitability for predicting properties of water clusters with varying size. Long-time SLEND/6-31G* (n = 1-4) simulations predict the formation of the DNA-damaging radicals H, OH, O and H3O. While "smallest-drop" isomers are included, no early manifestations of bulk water PCT properties are observed and simulations with larger water clusters will be needed to capture those effects. This study is the largest SLEND investigation on water radiolysis to date

In Honour of N. Yngve Öhrn: Surveying Proton Cancer Therapy Reactions with Öhrn\u27s Electron Nuclear Dynamics Method. Aqueous Clusters Radiolysis and DNA-Base Damage by Proton Collisions

© 2014 © 2014 Taylor & Francis. Proton cancer therapy (PCT) utilises high-energy H+ projectiles to cure cancer. PCT healing arises from its DNA damage in cancerous cells, which is mostly inflicted by the products from PCT water radiolysis reactions. While clinically established, a complete microscopic understanding of PCT remains elusive. To help in the microscopic elucidation of PCT, Professor Öhrn\u27s simplest-level electron nuclear dynamics (SLEND) method is herein applied to H+ + (H2O)3-4 and H+ + DNA-bases at ELab = 1.0 keV. These are two types of computationally feasible prototypes to study water radiolysis reactions and H+-induced DNA damage, respectively. SLEND is a time-dependent, variational, non-adiabatic and direct-dynamics method that adopts a nuclear classical-mechanics description and an electronic single-determinantal wavefunction. Additionally, our SLEND + effective-core-potential method is herein employed to simulate some computationally demanding PCT reactions. Due to these attributes, SLEND proves appropriate for the simulation of various types of PCT reactions accurately and feasibly. H+ + (H2O)3-4 simulations reveal two main processes: H+ projectile scattering and the simultaneous formation of H and OH fragments; the latter process is quantified through total integrals cross sections. H+ + DNA-base simulations reveal atoms and groups displacements, ring openings and base-to-proton electron transfers as predominant damage processes