Elucidating the Roles of Fenton Reactants in Drug-Treated Cells using a Selective Rhodamine-Thiophenol Fluorogenic Sensor

Abstract

While Fenton chemistry has long been known to play a role in inducing cellular stress, there has been recent renewed interest in understanding its roles in health and disease. Here we describe a fluorogenic probe, RTFt1, which applies both chelation and recognition strategies to sense the Fenton reactants, Fe(II) and H2O2. RTFt1 undergoes a 200-fold increase in red fluorescence emission in the presence of both Fe(II) and H2O2. After confirming the suitability of this new probe in cellular models, we demon-strated its utility in sensing the Fenton chemistry that accompanies ferroptosis and cisplatin-induced cytotoxicity. We found that levels of the Fenton reactants increased when cells were treated with cisplatin or co-treated with cisplatin and tubastatin A. This points to a role for Fenton chemistry in the cytotoxic effects of these treatments. We expect that RTFt1 will be able to provide a deeper understanding of Fenton reactants more broadly in biological systems.