Choudhary_2025_Chem.Commun.(Camb)__

Hydrogen sulfide (H(2)S) and sulfane sulfur species such as persulfides and polysulfides protect the cells from oxidative stress and are central to the endogenous antioxidant response. Here, we designed and developed a tool that is cleaved by esterase to generate phenacylthiol, which is an artificial substrate for 3-mercaptopyruvate sulfurtransferase (3-MST) and non-electrophilic lactone as a by-product. The esterase-sensitive persulfide generator enhances H(2)S and sulfane sulfur and protects chondrocytes from the lethality induced by elevated reactive oxygen species (ROS).