Carbon Monoxide Donors: From Synthetic Applications to Reassessment of Commercially Available Compounds

Author ORCID Identifier

Date of Award


Degree Type


Degree Name

Doctor of Philosophy (PhD)



First Advisor

Binghe Wang

Second Advisor

Jun Yin

Third Advisor

Maged Henary


Carbon monoxide (CO) is known for various reasons. The general public sees CO as the “silent killer”, while organic chemists see CO as a reagent for carbonylation, and medicinal chemists and biologists see CO as an endogenous signaling molecule with therapeutic potential. Along these lines, we have developed and assessed CO donors for wide ranging applications.

In terms of synthetic organic chemistry, our lab has developed a light-activated CO donor for Pd-catalyzed and light-mediated carbonylation. This low-molecular-weight, solid CO surrogate that only requires a low-power LED for activation to release 2 equivalents of CO can be universally implemented in various palladium-catalyzed carbonylative transformations. It is also compatible with protocols that employ blue-light to activate conventionally inaccessible substrates such as nonactivated alkyl halides.

In the focus of its medicinal and biological applications, CO is produced in mammals primarily through heme degradation mediated by heme oxygenases, HO-1 and HO-1, with the inducible form HO-1 being cytoprotective and immunomodulatory. Much of HO-1’s effects have been recapitulated by exogenous administration of CO and have been pharmacologically validated for its therapeutic benefits in animal models. For the further development of CO-based therapeutics, new delivery forms are needed to address the inherent limitations of using inhaled CO for therapeutic applications. Along this line, there have been metal-based CO-releasing molecules (CORMs), photo-sensitive organic donors, and organic CO prodrugs that release CO under physiological conditions. Among these, four commercially available carbonyl complexes with either a transition metal or borane (CORM-2, CORM-3, CORM-A1, and CORM-401) have played prominent roles appearing in over 650 publications. Detailed CO-releasing characteristics in buffer and cell culture media have been reported by various labs for the two ruthenium compounds: CORM-2 and CORM-3. In this work, we characterize the other two, CORM-A1 and CORM-401, for its CO release properties under various conditions important for its application in studying CO biology. Specifically, we report the idiosyncratic CO production and redox activity of CORM-A1, as well as the variable CO production and impure commercial samples of CORM-401.

This work highlights the foundational issues and unreliability of the commercially available CORMs including a lack or idiosyncratic CO production, CO-independent chemical and biological activity, and lack of good negative controls of the carrier. The significance of this work includes highlighting the convolution the CORMs have had caused in the CO field, as well as confronting the issues of influence from prominent researchers and commercial vendors.

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