Elucidating the Roles of Fenton Reactants in Drug-Treated Cells by 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 rhodamine-thiophenol 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 demonstrated 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.