A Tale of Two Cities in Fluorescent Sensing of Carbon Monoxide: Probes That Detect CO and Those That Detect Only Chemically Reactive CO Donors (CORMs), but Not CO

Carbon monoxide (CO) is endogenously produced with a range of pharmacological activities. Sensitive and selective detection of CO is critical to studying its biology. Since the first report of a CO fluorescent probe in 2012, more than 100 papers on this topic have appeared. Noteworthy in such work is the widespread use of two commercially available ruthenium–carbonyl complexes (CORM-2 and CORM-3) as CO surrogates. Unfortunately, these two CORMs are chemically very reactive and preferentially release CO₂ but not CO, unless in the presence of a nucleophile. As a result, there are “two tales” of the reported CO probes: those that detect CO and those that detect only the CORM used but not CO. In addition, because of their lack of reliable CO production and fast degradation in an aqueous solution, there is the question of what “detecting CORM-2 or CORM-3” really means in the context of CO research. Additionally, for applying fluorescent CO probes in detecting low levels (often nanomolar) of CO in vivo, fast reaction kinetics is a prerequisite for meaningful results. In this Perspective, we discuss in detail these issues with the understanding of the evolutionary nature of scientific discoveries and the aim of preventing further confusion.