Sensing of Biological Fenton Chemistry and Elucidation of Drug-induced Intracellular Fenton Biochemistry Alteration

While Fenton chemistry, Fe(II) + H₂O₂ à OH^– + ^●OH, has long been known to play a role in inducing cellular stress, recent decades have seen an increasing appreciation for the roles of the Fenton reaction in both health and disease. However, the roles that Fenton chemistry plays in pathological processes remain unclear. Although the two analytes of Fenton chemistry can be sensed individually, there is no fluorescent probe that simultaneously senses the two Fenton reactants. Such a probe would enable differentiation of Fenton chemistry from other conditions that induce changes in either Fe(II) or H₂O₂. To fill this technology gap we developed a novel small molecule fluorogenic probe for Fenton biochemistry, RTFt1. After confirming the suitability of this new probe in cellular models, we demonstrated its utility in sensing the Fenton chemistry accompanying ferroptosis and cisplatin-induced cytotoxicity. Having been applied to sense Fenton chemistry in several biological models, we envisage this probe will be useful in further uncovering an understanding of the physiological roles of this chemistry.