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

Thioether oxidation to sulfoxide by HO 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 HO oxidation under near-physiological conditions is expected to have half-lives on the scale of hundreds of hours at pathophysiologically relevant HO 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 HO in activating thioether-based drug delivery systems.