Mechanistic Investigation on Oxidative Degradation of ROS-Responsive Thioacetal/Thioketal Moieties and Their Implications

Abstract

Summary Thioacetal/thioketal moieties have been identified as responsive to reactive oxygen species (ROS). Despite its utility in a broad range of applications, the mechanism that underlies the ROS-induced cleavage of these moieties is not well understood. In this work, through a series of structure-property relationship studies such as Hammett correlation, we propose a mechanism or the oxidative cleavage of thioacetals and thioketals, where the thiolate components are converted to the corresponding disulfide product along with the formation of the respective aldehydes and ketones. The mechanism proposed here involves thioether oxidation that leads to the formation of a thionium intermediate, hydrolysis of which leads to the aldehyde/ketone product. In addition, we also show a preliminary demonstration of the utility of such an understanding, as it offers to sequentially release two distinct small molecules caged in a substrate using two contradictory stimuli, viz. oxidative and reductive conditions.