On the Question of Uncatalyzed CO Insertion into a Hydrazone Double Bond: A Comparative Study Using Different CO...

Because of endogenous signaling roles of carbon monoxide (CO) and its demonstrated pharmacological effects, there has been extensive interests in developing fluorescent CO probes. Palladium-mediated CO insertion has been successfully used for such applications. However, recent years have seen many publications of using uncatalyzed CO insertion into a hydrazone double bond as a way to sense CO. Such chemistry has no precedents otherwise. Further, the rigor of the CO-sensing work was largely based on using ruthenium-carbonyl complexes such as CORM-3 as CO surrogates, which have been reported to have extensive chemical reactivity and to release largely CO₂ instead of CO unless in the presence of a strong nucleophile such as dithionite. For all of these, it is important to reassess the feasibility of such a CO-insertion reaction. By studying two of the reported "CO probes" using CO gas, this study finds no evidence of CO insertion into a hydrazone double bond. Further, the chemical reaction between CO gas and a series of eight hydrazone compounds was conducted, leading to the same conclusion. Such findings are consistent with the state-of-the-art knowledge of carbonylation chemistry and do not support uncatalyzed CO insertion as a mechanism for developing fluorescent CO probes.