Tetrathiatriarylmethyl (TAM) radicals are commonly used as oximetry probes for electron paramagneticresonance imaging applications. In this study, the electronic properties and the thermodynamic preferencesfor O
2 addition to various TAM-type triarylmethyl (trityl) radicals were theoretically investigated. Theradicals' stability in the presence of O
2 and biological milieu was also experimentally assessed usingEPR spectroscopy. Results show that H substitution on the aromatic ring affects the trityl radical's stability(tricarboxylate salt
1-CO2Na > triester
1-CO2Et > diester
2-CO2Et > monoester
3-CO2Et) and maylead to substitution reactions in cellular systems. We propose that this degradation process involves anarylperoxyl radical that can further decompose to alcohol or quinone products. This study demonstrateshow computational chemistry can be used as a tool to rationalize radical stability in the redox environmentof biological systems and aid in the future design of more biostable trityl radicals.