Probing oxidative stress: Small molecule fluorescent sensors of metal ions, reactive oxygen species, and thiols

► ROS, thiols, and metals (redox and non-redox active) play roles in oxidative stress. ► Fluorescent sensors of these molecular players of oxidative stress are reviewed. ► Intricacies and complications in sensor design and implementation are highlighted. ► Multifunctional sensors that respond to ROS and metal ions are described. Oxidative stress is a common feature shared by many diseases, including neurodegenerative diseases. Factors that contribute to cellular oxidative stress include elevated levels of reactive oxygen species, diminished availability of detoxifying thiols, and the misregulation of metal ions (both redox-active iron and copper as well as non-redox active calcium and zinc). Deciphering how each of these components interacts to contribute to oxidative stress presents an interesting challenge. Fluorescent sensors can be powerful tools for detecting specific analytes within a complicated cellular environment. Reviewed here are several classes of small molecule fluorescent sensors designed to detect several molecular participants of oxidative stress. We focus our review on describing the design, function and application of probes to detect metal cations, reactive oxygen species, and intracellular thiol-containing compounds. In addition, we highlight the intricacies and complications that are often faced in sensor design and implementation.