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. 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 among endogenous gaseous signaling molecules and low dosing 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 majority of CO produced in mammals originates from the degradation of heme by the three isoforms of heme oxygenase, whereby HO-1 is induced by oxidative stress, CO, and an array of xenobiotics. HO-2 and HO-3 are constitutive. Other endogenous sources may include lipid peroxidation, 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. 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. The majority of therapeutically relevant CORMs are transition metal complexes primarily based on iron, molybdenum, ruthenium, manganese, cobalt, and rhenium The release of CO from carrier agents can be induced photochemically. These carriers are called photoCORMs and include both metal complexes and metal-free (organic) compounds of various structural motifs which could be regarded as a special type of photolabile protecting group. Enyzme triggered CORMs (ET-CORMs) have been developed to improve selective local delivery of CO. Some ET-CORM prodrugs are activated by esterase enyzmes for site specific liberation of CO. Organic small molecules are being developed to overcome toxicity limitations of inorganic CORMs. Methylene chloride was the first organic CORM orally administered based on previous reports of carboxyhemoglobin formation via metabolism. The second organic CORM, CORM-A1 (sodium boranocarbonate), was developed based on a 1960s report of CO release from potassium boranocarbonate.