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

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Abstract

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.

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Acknowledgements

The authors gratefully acknowledge financial supports from the National Institutes of Health (DK119202 on CO and colitis; and DK128823 on CO and acute kidney injury), the Georgia Research Alliance Eminent Scholar endowment fund (BW), the Dr. Frank Hannah endowment fund (BW) and internal resources at Georgia State University. NB acknowledges the support of the Brains and Behavior Program through a graduate B&B fellowship. The authors would also like to acknowledge Jordan Dinning and Dr. Todd Harrop at the University of Georgia for their contributions in the EPR experiments.

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  1. These authors contributed equally: Nicola Bauer, Qiyue Mao

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  1. Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA, 30303, USA

    Nicola Bauer, Qiyue Mao, **aoxiao Yang & Binghe Wang

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Bauer, N., Mao, Q., Yang, X. et al. Characterization of the CO release properties of a common CO donor, CORM-401, in the context of its application in studying CO biology. Med Chem Res (2024). https://doi.org/10.1007/s00044-024-03221-3

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