To further corroborate the mechanism and to find the optimized ratio of organochloride to oxygen, we constructed a mathematic model to simulate the organoperoxyradical generation pathway. The model is composed of coupled differential equations (equation 1 to 5) which describe the reaction kinetics of species formation in the network. At room temperature, the reaction rate of aqueous electrons and oxygen (k3) has been reported to be 1.9×10 10 M -1 s -1 . We used the reaction rate of chloroform and aqueous electrons (3.0×10 10 M -1 s -1 ) 20 as the value for k1 since TCE has the same trichloro-group. For the rate of the carbon-centred radical and oxygen (k2), we used 3.3×10 9 M -1 s -1 which is the rate of trichloromethyl radical and oxygen. The approximated values of k1 and k2 may lead to an imprecise calculation of the final yield of M2, but using approximate values will allow prediction of trend in these reaction networks. The chemical reactions in the network occur at the end of physicochemical stage (ca. 10 -12 sec) when aqueous electrons are in thermal equilibrium with the liquid. So, the producing rate of aqueous electron, as shown in the constant term of equation 4, is calculated from the dose rate (0.108 Gy s -1 ) multiplying the G-value of aqueous electron (0.28×10 -6 M Gy -1 ). We set up the starting concentration of oxygen and TCE and the model calculated the numerical solution of [M2] at t = 555 sec, corresponding to the yield of M2 after 60 Gy of irradiation. We plotted the simulated yields of M2 against different starting concentrations of TCE and oxygen in Figure . The oxygen content is expressed as both concentration (µM) and partial pressure (%) according to a linear relationship (256 µM = 21%). At a high concentration of oxygen, the yield of M2 decreases with decreasing concentration of TCE, which is in line with the trend as shown in Figure . At low oxygen concentration (e.g. from 10 µM to 25 µM), the yield of M2 slightly decreases when going from 500 µM to 50 µM TCE, followed by a sharp drop from 50 µM to 0 µM TCE. At very low oxygen concentration, the scavenging of aqueous electrons by oxygen becomes insignificant, resulting in a 90% of the maximum M2 yield at low TCE concentration (e.g. 2% oxygen and 100 µM TCE). Oxygen concentration lower than 10 µM results in low yield of M2 at any TCE concentration. It should be noted that the average physiological oxygen level in normal tissues is around 5% (61.0 µM) while that in cancerous tissues is around 2% (24.4 µM). Although some types of tumours are extremely hypoxic (lower than 0.5% oxygen where the formation of M2 will be less than 2 µM at any [TCE]), the simulated results show that the organochloride mediated oxidation can occur in most tumours, with increased efficiency in hypoxic environments. To achieve a high yield of M2, TCE must be present in large excess. For example, the lowest limit of [TCE] to achieve 90% of the maximum yield is 46 µM. Moreover, by tuning the concentration of organochloride, healthy tissues with high oxygen concentrations can be less affected by the radiation induced oxidation. For instance, at 26 µM TCE, the yield of M2 is 11.2 µM at 2% oxygen while the yield is 6.64 µM at 5% oxygen. We also see the limitations of the mathematic model and results from experiment. For example, as the model only includes the key reactions of the network, side reasons such as the radical recombination or deactivation of M1 or M2 are not considered, which could lead to a lower yield of compound 2 and an increasing difference between modelling data and experiments at low [TCE]. Rate constants k1 and k2 can be measured by pulse radiolysis techniques to precisely predict the yield. Besides, 1 H NMR is not sensitive enough to detect low concentrations of the probe, so the yields at 10 µM TCE are undetectable (Figure ). Also, regulating oxygen concentrations in aqueous solution is challenging and that could cause large variation, especially at low TCE concentration. Still, the model describes general trends in line with experimental data and as such can be used to predict system behavior. We then investigated the viability of using thioether-based compound as caging group of radiation sensitive prodrugs. As a model compound, 2,2'-thiodiacetic acid (compound 3) was exposed to 60 Gy of 𝛾-irradiation in PBS/12 mM TCE. As shown in Figure , two doublet peaks were observed from 3.78 to 3.63 ppm, which correspond to the heterogeneous protons (Ha and Hb) of compound 4 (Figure ). The oxidation of compound 3 makes it possible to be used as radiation-sensitive linkers, as the β-sulfoxide esters are more labile to hydrolysis, resulting the de-caging of a hydroxyl group (Figure ). Camptothecin (CPT) has been used as anti-cancer drugs since 1960s, where the lactone ring and 20-OH group are critical for topoisomerase I inhibiting activity. However, the 20-OH involves the nucleophilic ring-opening of the lactone, resulting a poor stability in cyto-plasma and less activity in vivo. We synthesized a CPT-based prodrug, TA-CPT, where the 20-OH was protected by compound 3 via an ester group (Figure ). The release of CPT under various treatments was monitored by high-performance liquid chromatography (HPLC, Figure ), and the conversion from TA-CPT to CPT was summarized in Figure . TA-CPT hydrolysed slowly in PBS, while adding 1 mM H2O2 increased the hydrolysis rate. TA-CPT sulfoxide was not observed, indicating the oxidation of TA-CPT is rate-determining step. After irradiating for 60 Gy in PBS/12 mM TCE and incubating for 10 min, more than 20% of TA-CPT was converted to CPT, which is significantly higher than that of H2O2 treatment, indicating a quick oxidation and release of CPT. The release rate of the irradiated group is similar to the PBS group. Irradiating for 8 Gy demonstrated the same trend as the 60 Gy group, meaning that drug release could also work for low-dose radiation. Our results demonstrate that compound 3 can be used as the radiation sensitive caging group in the presence of organochloride.