Thioether Oxidation Chemistry in Reactive Oxygen Species (ROS)-Sensitive Trigger Design: A Kinetic Analysis

Thioether oxidation to sulfoxide by H₂O₂ has been widely reported as an ROS-sensitive trigger in drug delivery applications. Through a number of straightforward kinetic experiments with a series of aryl thioethers, we show that H₂O₂ oxidation under near-physiological conditions is expected to have half-lives on the scale of hundreds of hours at pathophysiologically relevant H₂O₂ concentrations. On the other hand, hypochlorite can oxidize thioethers at much faster rates with half-lives in the range of seconds to sulfoxide and minutes to sulfone under similar conditions. Such information means that hypochlorite likely plays a much more important role than H₂O₂ in activating thioether-based drug delivery systems.