A Cu(II)-Based Fluorescent Probe for Carbon Monoxide, Nap-BC-Cu(II), Does Not Selectively Detect Carbon Monoxide

Reports of carbon monoxide (CO) pharmacology have spurred intense interest in developing its fluorescent probes with much success. However, one unfortunate event in this area is the wide-spread use of chemically reactive metal/BH₃-CO complexes as "CO-releasing molecules" or CORMs that do not produce CO or produce CO in an idiosyncratic fashion. Consequently, a large number of reported fluorescent "CO probes" only respond to the CORM used, but not to CO. Though most of these issues have been clarified in the literature, there is a surprising recent publication on a Cu(II)-based fluorescent "CO probe," Nap-BC-Cu(II), relying on undefined chemical principles. We reassessed the ability for Nap-BC-Cu(II) to detect CO and found no evidence for Nap-BC-Cu(II) to selectively detect CO at even non-physiologically relevant high concentrations (high micromolar) of CO. Marginal effects were observed only when CO was continuously bubbled through the "probe" solution for 15 min. Further, Nap-BC-Cu(II) was found to be sensitive to ascorbic acid and cysteine. Overall, this probe did not respond to CO in a pathophysiologically relevant context. Our findings do not support the notion of Nap-BC-Cu(II) being a CO probe for studying CO biology. We hope this will be the last of this saga of "CO probes" that do not afford selective detection of CO, largely due to the confusions caused by using chemically reactive CORMs.