Reaction network analysis of organochloride mediated oxidation induced by ionizing radiation

The generation of organoperoxy radical by irradiating aqueous solutions of organochlorides depends on the concentration of organochloride, where low concentration results in low yield of reactive oxygen species (ROS). The need of high concentration of organochloride limits the application in cancer therapy as most small molecule organochlorides show liver toxicity at elevated concentrations. To study if the oxidation is feasible at low concentration of organochloride, we proposed a reaction network where the effect of molecular oxygen is included. We hypothesized that oxygen competes with the organochloride to react with aqueous electrons, thereby causing a low yield of ROS at low organochloride concentrations. However, oxygen is necessary in the ROS formation pathway, which complicates straightforward prediction of reaction outcome. We developed a mathematic model to simulate the yield of ROS depending on organochloride and oxygen concentrations. The simulated results indicate that at low organochloride concentration, decreasing oxygen concentration leads to higher yield of ROS, with a peak at approximately 2% partial pressure of oxygen, and oxygen lower than 2% results in a sharp yield drop of ROS. Experiments using a thioether as reductant to quantify the ROS formation show good agreement with simulated data, verifying the proposed network. After irradiation in phosphate buffer saline/organochloride, a thioether caged drug showed efficient uncaging yield, demonstrating the viability of using thioether as a radiation-sensitive group.