Carbon monoxide (CO), a silent and powerful poison gas, might actually lend itself for a variety of promising clinical applications, according to the researchers from Sheffield University in the UK. Professor Brian Mann and colleagues from the University’s Department of Chemistry and hemoCORM Ltd, a spinout company, are working on water-soluble molecules that can deliver CO to tissues to “reduce inflammation, widen blood vessels, increase blood flow, prevent unwanted blood clotting and even suppress the activity of cells and macrophages which attack transplanted organs,” according to the university’s press release.
hemoCORM explains the CO-RM molecules technology:
Carbon monoxide (CO) is the most commonly encountered environmental poison. Paradoxically, more than half a century ago, it was found that CO is constantly formed in humans in small quantities, and that under certain pathophysiological conditions this endogenous production of CO may be increased. The discovery that hemoglobin, a heme-dependent protein, is required as a substrate for the production of CO in vivo, and the identification of the enzyme heme oxygenase as being crucial for the generation of this gas in mammals, set the basis for the early investigation of an unexpected role of CO in the vasculature.
The subsequent characterization of constitutive (HO-2) and inducible (HO-1) isoforms of heme oxygenase, as well as studies on the kinetics and tissue distribution of these enzymes, started to reveal a major importance of this pathway in the physiological degradation of heme and the realisation that the end products of heme degradation (CO, biliverdin and bilirubin) possess crucial biological activities.
The work of many research groups has confirmed that CO has a physiological role in all major organ systems, from maintaining vascular tone through neurotransmission, to glycaemic control in the pancreas. Further involvement in pathophysiological processes has raised the possibility that exogenous administration of CO in some form, could be the basis of novel therapeutic approaches…
Metal carbonyl CO-RMs
Our pioneering work started with the discovery that compounds such as Fe(CO)5, Mn2(CO)10, and [RuCl2(CO)3]2 have the ability to release CO and provoke the physiological reactions expected of CO gas. We termed these compounds “carbon monoxide-releasing molecules” (CO-RMs).
Several generations of CO-RMs have since been developed, which have better solubility properties and a range of rates of CO-release. An example of these is the ruthenium centred CORM-3 – Ru(CO)3Cl(glycinate) – the properties of which were initially described in 2003 and have subsequently been confirmed many publications.
Subsequently, numerous additional CO-RMs have been synthesized and studied, which are the subject of unpublished patent applications.
These have been developed in collaboration with Prof. Roger Alberto of the University of Zurich. The prototype molecule is CORM-A1 (sodium boranocarbonate).
Company’s white paper is below.
Press release: Chemistry turns killer gas into potential cure …