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.

Low degrees of symmetry breaking in initial states lead to full-blown symmetry breaking and improved predictions in time-dependent direct dynamics.

Proton cancer therapy (PCT) utilizes high-energy proton projectiles to obliterate cancerous tumors with low damage to healthy tissues and without the side effects of X-ray therapy. The healing action of the protons results from their damage on cancerous cell DNA. Despite established clinical use, the chemical mechanisms of PCT reactions at the molecular level remain elusive. This situation prevents a rational design of PCT that can maximize its therapeutic power and minimize its side effects. The incomplete characterization of PCT reactions is partially due to the health risks associated with experimental/clinical techniques applied to human subjects. To overcome this situation, we are conducting time-dependent and non-adiabatic computer simulations of PCT reactions with the electron nuclear dynamics (END) method. Herein, we present a review of our previous and new END research on three fundamental types of PCT reactions: water radiolysis reactions, proton-induced DNA damage and electron-induced DNA damage. These studies are performed on the computational prototypes: proton + H2O clusters, proton + DNA/RNA bases and + cytosine nucleotide, and electron + cytosine nucleotide + H2O. These simulations provide chemical mechanisms and dynamical properties of the selected PCT reactions in comparison with available experimental and alternative computational results.

As dinâmicas da desidratação do álcool protonado (R)-3,3-dimetilbutan-2-ol (álcool pinacolil), [(CH 3 ) 3 C-CH(OH 2 )CH 3 ] + , e da cicloadição eteno + 1,3-butadieno foram estudadas com a técnica de dinâmica molecular direta de Born-Oppenheimer (BOMD) usando o método AM1. Mais de 10.000 trajetórias foram geradas, em que a maioria foi utilizada no procedimento ainda não explorado de recozimento simulado/fragmentação (SA/F). A energia potencial obtida com o método AM1 (PES-AM1) para o álcool protonado apresenta dois estados de transição associados ao intermediário complexo [(CH 3 ) + foi praticamente inexistente durante a dinâmica. Apesar do caminho concertado (dissociação do fragmento H 2 O e migração do grupo CH 3 ) não ser uma coordenada de reação intrínseca (IRC) no método PES-AM1, um número significativo de trajetórias envolveu este caminho. Para a reação de Diels-Alder, mesmo partindo-se do estado de transição simétrico, e utilizando uma função de onda AM1 restrita, a dinâmica forneceu um número significativo de trajetórias que seguiram caminhos assimétricos, isto é, não-IRC, em direção ao ciclohexeno, independentemente do procedimento utilizado na inicialização. E notável ainda que todas estas trajetórias que seguiram caminhos assimétricos envolveram um caminho de reação concertado.The dynamics of dehydration of the protonated (R)-3,3-dimethylbutan-2-ol (pinacolyl alcohol), [(CH 3 ) 3 C-CH(OH 2 )CH 3 ] + , and of ethene + 1,3-butadiene cycloaddition were studied with the BornOppenheimer molecular dynamics (BOMD) technique for direct dynamics using the AM1 method. More than 10,000 trajectories were generated, most of them related to the unexplored simulated annealing/fragmentation approach. The AM1 potential energy surface (PES) for the protonated pinacolyl alcohol presents two transition states related to the [(CH 3 ) 3 C-CHCH 3 ] + ···OH 2 intermediate complex and to CH 3 migration leading to the [(CH 3 ) 2 C-CH(CH 3 ) 2 ] + ···OH 2 product complex. Direct dynamics yielded negligible trajectories involving these complexes, since the momentum acquired by the H 2 O fragment led to a complete dissociation. Thus, rearrangement of the secondary carbocation [(CH 3 ) 3 C-CHCH 3 ] + was practically inexistent during the dynamics. Despite the concerted path (H 2 O dissociation and CH 3 migration) not being an IRC (intrinsic reaction coordinate) path in AM1-PES, a statistically significant number of trajectories involved this path. As for the Diels-Alder reaction, even when started from a symmetric transition state using the spin restricted AM1 wavefunction, the dynamics yielded a significant number of trajectories that followed asymmetric, i.e. non-IRC, paths toward cyclohexene, independent of the initialization approach. It is noteworthy that all these asymmetric path trajectories led to a concerted reaction mechanism.Keywords: protonated pinacolyl, ethene + 1,3-butadiene, cycloaddition, non-IRC IntroductionRecently, time-dependent methods, 1,2 particularly direct dynamics classical trajectory ones, 3,4 have be...

In a recent paper [Phys. Rev. A 77, 064702 (2008)], Bruhns et al. reported on an experimental investigation of charge transfer in collisions of Si 3+ ions with atomic hydrogen and compared the energy dependence of the transfer cross sections with published theoretical results and with earlier experimental results for other effectively-one-electron isocharged ions, including C 3+ and O 3+ . These authors observe that these three ions all have the structure of a single electron outside a closed subshell and thus might be expected to behave similarly. However, their results show quite different behavior, and they conclude that the influence of quantum-mechanical effects from the ionic core is clearly seen. We have investigated theoretically three collision systems, Si 3+ , C 3+ , and O 3+ with atomic hydrogen, at projectile energies up to 10 keV/amu using the method of electron nuclear dynamics (END). In this paper we want to clarify and describe in some detail these quantum-mechanical effects by showing the time-dependent dynamics of the electrons during the collision of these three ions with atomic hydrogen. Total charge transfer cross sections were calculated for all three ions and compared with other theoretical and experimental results, showing good overall agreement. With this validation of the END description of the processes, we analyze the details of the computed dynamics of the electrons in each of the processes and illustrate the different mechanisms underlying observed differences in reaction outcomes.