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Carbon monoxide-releasing molecules (CO-RMs) are chemical compounds that release controlled amounts of carbon monoxide (CO) to cells and tissues and are being developed as potential therapeutic agents. Although long recognized as a poison, CO also exhibits beneficial effects in small doses. These effects include anti-inflammatory activity, vasodilatation, and cardioprotection. CO is produced in mammals during the degradation of heme by heme oxygenase-1, a redox-sensitive enzyme induced by oxidative stress. It is this enzymatic reaction that inspired the development of synthetic CO-RMs. Therapeutic drugs have historically been developed based on the similar activity of small molecules in biological signaling, examples exist in the case of both H2S and NO-releasing drugs.
Synthetic CO-RMs are typically metal carbonyl complexes. A representative CO-RM that has been extensively characterized both from a biochemical and pharmacological view point is the ruthenium(II) complex Ru(glycinate)Cl(CO)3, also known as CORM-3.
Testing of Ru(glycinate)Cl(CO)3
Studies have yielded evidence suggesting that high concentrations of CO in cellular medium can both inhibit or stimulate cellular respiration. In testing where high concentrations of CORM-3 were used (125-250 μM) E. coli respiration was considerably inhibited. But when the CORM-3 was tested in with cells placed in an O2 incubation chamber, so as to provide conditions mirroring normal cellular CO:O2 ratios, a 100 μM addition of CORM-3 stimulated respiration. Although CORM-3 doesn't show consistent results as successful inhibitor of cellular respiration it gives an understanding of fundamental reactivity of CO-RMs in biological systems.