![]() ![]() 18–20 Furthermore, photodissociation and consequent elimination of the CO group(s) following exposure to light has been reported in the case of specific metal carbonyls. 17 From inorganic chemical studies conducted on these substances in vitro, it is known that certain ligands in a metal complex can promote, either sterically or electronically, dissociation of CO. These complexes are compounds that contain a heavy metal such as nickel, cobalt, or iron surrounded by carbonyl (CO) groups as coordinated ligands. Our laboratory has been working for the past few years on the characterization of transition metal carbonyls as potential CO-releasing molecules (CO-RMs). ![]() Research in the field of NO has been largely facilitated by the development of a variety of organic compounds that spontaneously release NO and can reproduce a physiological or pathophysiological function of NO however, no attempts have been made so far to identify compounds that are capable of carrying and delivering CO into biological systems. It is interesting that many of the novel properties pertaining to CO have strong analogies with the well-established biological activities elicited by nitric oxide (NO), another gaseous molecule produced intracellularly by a family of ubiquitous enzymes known as NO synthases. Thus, consistent findings reveal a series of important cellular functions that support a versatile and previously unidentified role for CO. 10,11 In addition, exogenously applied CO has been shown to protect against lung injury in vivo, 12,13 prevent both production of proinflammatory cytokines 14 and endothelial cell apoptosis, 15 and suppress graft rejection in mouse-to-rat cardiac transplants 16 all these effects are simulated by transfection of the HO-1 gene. 2–4 As part of its physiological and cytoprotective actions, heme oxygenase-derived CO appears to play a major role as neurotransmitter, 5–7 regulator of sinusoidal tone, 8 inhibitor of platelet aggregation, 9 and suppressor of acute hypertensive responses. 2 There is general consensus, supported by extensive published reports, that HO-1 represents a pivotal inducible defensive system against stressful stimuli, including UVA radiation, carcinogens, ischemia-reperfusion damage, endotoxic shock, and several other conditions characterized by production of oxygen-derived free radicals. The main endogenous source of CO is heme oxygenase, which exists in constitutive (HO-2 and HO-3) and inducible (HO-1) isoforms heme serves as substrate for HO-1 and HO-2 in the formation of CO, free ferrous iron, and biliverdin, the latter being rapidly converted to bilirubin by biliverdin reductase. Īlthough it has been known for a long time that carbon monoxide (CO) is generated in the human body, 1 only in recent years have scientists begun to explore the possible biological activities of this gaseous molecule. The full text of this article is available at. In the long term, transition metal carbonyls could be utilized for the therapeutic delivery of CO to alleviate vascular- and immuno-related dysfunctions. Thus, we have identified a novel class of compounds that are useful as prototypes for studying the bioactivity of CO. These vascular effects were mimicked by induction of HO-1 after treatment of animals with hemin, which increases endogenously generated CO. Moreover, CO-RMs caused sustained vasodilation in precontracted rat aortic rings, attenuated coronary vasoconstriction in hearts ex vivo, and significantly reduced acute hypertension in vivo. Specifically, spectrophotometric and NMR analysis revealed that dimanganese decacarbonyl and tricarbonyldichlororuthenium (II) dimer release CO in a concentration-dependent manner. We report that a series of transition metal carbonyls, termed here carbon monoxide-releasing molecules (CO-RMs), liberate CO to elicit direct biological activities. ![]() Carbon monoxide gas is known to dilate blood vessels in a manner similar to nitric oxide and has been recently shown to possess antiinflammatory and antiapoptotic properties. Customer Service and Ordering InformationĬarbon monoxide (CO) is generated in living organisms during the degradation of heme by the enzyme heme oxygenase, which exists in constitutive (HO-2 and HO-3) and inducible (HO-1) isoforms.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB). ![]()
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