<p>Oxasaphosphole can activate the triplet dioxygen, similar to biological systems, where the formed hydroperoxide is the key oxidative species of oxidation processes. The oxidation of cysteine and thiophenol by oxasaphosphole (Oxp) showed significant differences according to the solvent media, which has been studied theoretically. DFT calculations are a powerful tool to reveal the experimentally proposed mechanisms and give a closer look into the details of how the solvent molecules’ orientation and weak interactions significantly influence the intermediates and transition states. Furthermore, the activation of dioxygen was also studied, and the experimentally not observable steps were explained by the theoretical calculations where the cluster and separate molecule models showed very good correlations in terms of energetics.</p> Graphical abstract <p></p>