Thioether Oxidation Chemistry in Reactive Oxygen Species (ROS)-Sensitive Trigger Design: A Kinetic Analysis
Thioether oxidation to sulfoxide by H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> oxidation under near-physiological conditions is expected to have half-lives on the scale of hundreds of hours at pathophysiologically relevant H<sub>2</sub>O<sub>2</sub> 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 H<sub>2</sub>O<sub>2</sub> in activating thioether-based drug delivery systems.
Authors
- Giovanni Gadda (ORCID: https://orcid.org/0000-0002-7508-4195)
- Shameer M. Kondengadan (ORCID: https://orcid.org/0000-0003-0791-6380)
- Joanna Afokai Quaye (ORCID: https://orcid.org/0000-0002-7041-4570)
- Binghe Wang (ORCID: https://orcid.org/0000-0002-2200-5270)
- Shubham Bansal (ORCID: https://orcid.org/0000-0003-3603-5099)
- A. Abdel‐Fattah
Institutions
- Georgia State University (US)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-03-19
- DOI
- https://doi.org/10.1021/acs.orglett.5c00747
- Citations
- 15
- Primary Topic
- Free Radicals and Antioxidants
- Type
- article
- Field-Weighted Citation Impact
- 14.04
Funders
- Georgia Research Alliance
- Georgia State University
- National Institute of Diabetes and Digestive and Kidney Diseases