Carbon monoxide-releasing molecules

Carbon monoxide-releasing molecules (CORMs) are chemical compounds designed to release controlled amounts of carbon monoxide (CO). CORMs are being developed as potential therapeutic agents to locally deliver CO to cells and tissues, thus overcoming limitations of CO gas inhalation protocols. CO is best known for its toxicity in carbon monoxide poisoning at high doses. However, CO is a gasotransmitter and supplemental low dosage of CO has been linked to therapeutic benefits. Pre-clinical research has focused on CO's anti-inflammatory activity with significant applications in cardiovascular disease, oncology, transplant surgery, and neuroprotection. The simplest source of CO is from a combustion reaction via burning sources such as fossil fuels or fire wood. Sources releasing CO upon thermal decomposition or combustion are generally not considered CORMs. Therapeutic interest in CO dates back to the study of factitious airs (hydrocarbonate) in the 1790s by Thomas Beddoes, James Watt, James Lind, Humphry Davy, Tiberius Cavallo and many others. Nickel tetracarbonyl was the first carbonyl-complex used to achieve local delivery of CO and was the first CO delivery molecule suggested to have therapeutic potential in 1891. The acronym CORM was coined in 2002 which marks the first modern biomedical and pharmaceutical initiative. The enzymatic reaction of heme oxygenase inspired the development of synthetic CORMs. The first synthetic CORMs were typically metal carbonyl complexes. A representative CORM that has been extensively characterized both from a biochemical and pharmacological view point is the ruthenium(II) complex Ru(glycinate)Cl(CO)3, commonly known as CORM-3. Therapeutic data pertaining to metallic CORMs are being reappraised to elucidate if observed effects are actually due to CO, or, if metal reactivity mediates physiological effects via thiol depletion, facilitating reduction, ion channel blockage, or redox catalysis. Despite questions pertaining to transition metals, pure CO gas and alternative non-metallic CO prodrugs and drug delivery devices have confirmed CO's therapeutic potential.