Characterization of the CO release properties of a common CO donor, CORM-401, in the context of its application in studying CO biology

In studying CO for its pathophysiological roles, four metal/borane-carbonyl complexes have been widely used as CO-releasing molecules (CORMs) because of their commercial availability. The CO-release properties of CORM-2, CORM-3, and CORM-A1 have been rigorously characterized. In this study, we characterize CORM-401 for its CO-donating ability under various conditions relevant to studying CO biology. First, with regard to the “intrinsic” CO-release ability of CORM-401 and factors that could influence such ability, we found significant effects of added reagents such as thiol, peroxide, and dithionite on CO-release yields and rate. The variable nature of CO release from CORM-401 indicates the need for predetermining CO production yield and rate under the same conditions before biology experiments. Second, because of the commercial availability of CORM-401 in DMSO stock solution, we characterized its stability in such a preparation and found significantly diminished CO-release capacity of CORM-401 after exposing to DMSO or aqueous solution. Third, because carboxyhemoglobin (COHb) is an important indicator of the ability for a CO donor to supply CO in animal model work, we characterized the property for CORM-401 to elevate COHb. Fourth, quality assurance of such a metal complex is important to ensure consistency in results. Our findings indicate that the unstable nature of CORM-401 presents a quality assurance issue for end users. All these combined with the previously reported chemical reactivity of CORM-401could lead to intractable scenarios in obtaining meaningful results using CORM-401 that can be reasonably attributed to CO in biology experiments.