  We present a first-principles molecular dynamics (MD) simulation and expound
upon a mechanism of oxygen depletion hypothesis to explain the mitigation of
normal tissue injury observed in ultra-high-dose-rate (UHDR) FLASH
radiotherapy. We simulated damage to a segment of DNA (also representing other
bio-molecules such as RNA and proteins) in a simulation box filled with H$_2$O
and O$_2$ molecules. Attoseconds physical interactions (ionizations, electronic
and vibrational excitations) were simulated by using the Monte Carlo track
structure code Geant4-DNA. Immediately after ionization, {\it ab initio}
Car-Parrinello molecular dynamics (CPMD) simulation was used to identify which
H$_2$O and O$_2$ molecules surrounding the DNA-molecule were converted into
reactive oxygen species (ROS). Subsequently, the femto- to nano-second
reactions of ROS were simulated by using MD with Reactive Force Field (ReaxFF),
to illustrate ROS merging into new types of non-reactive oxygen species (NROS)
due to strong coupling among ROS. Time-dependent molecular simulations revealed
the formation of metastable and transient spaghetti-like complexes among ROS
generated at UHDR. At the higher ROS densities produced under UHDR, stranded
chains (i.e., NROS) are produced, mediated through attractive electric polarity
forces, hydrogen bonds, and magnetic dipole-dipole interactions among hydroxyl
(\ce{^{.}OH}) radicals. NROS tend to be less mobile than cellular biomolecules
as opposed to the isolated and sparsely dense ROS generated at conventional
dose rates (CDR). We attribute this effect to the suppression of bio-molecular
damage induced per particle track. At a given oxygen level, as the dose rate
increases, the size and number of NROS chains increase, and correspondingly the
population of toxic ROS components decreases.
