Chemical biology news from across RSC Publishing.
Instant insight: Don't blame the messenger
18 October 2007
Brian Mann and Roberto Motterlini of the University of Sheffield and Northwick Park Institute for Medical Research in Harrow, UK, react to carbon monoxide's bad press
Carbon monoxide has a deservedly bad reputation as a silent killer; it causes the death of many people each year. Yet, small quantities of the gas are essential for life.
As a result of heme oxidation, around 0.6 per cent of the hemoglobin circulating in blood has CO attached. This increases markedly for smokers, whose lungs trap CO from the smoke. A person breathes out around 6cm3 of CO generated from heme degradation every day, and this is increased by inflammatory conditions such as asthma and diabetes.
Carbon monoxide is generated naturally in the body where it acts as a signalling molecule
CO functions as a signalling molecule in the body and it is especially important in the cardiovascular system. It possesses a wide range of bioactivities and beneficial effects, including protection against reperfusion injury, which occurs as the blood supply returns to a tissue following interruption (ischaemia). CO also suppresses organ rejection after transplantation and can reverse hypertension.
The beneficial biological activity of CO gas and its therapeutic potential have been demonstrated in animal experiments. However, delivering CO in this way requires very careful monitoring to prevent a dangerous dose being inhaled and unwanted exposure of the medical staff handling the gas. CO inhalation relies on the heme in blood transporting the CO from the lungs and exposes the whole body to increased CO levels, raising concerns about damage elsewhere.
A safer procedure would be to administer CO as a solution or in a solid form that subsequently releases the CO needed. This technique is well established for NO, which also acts as a signalling molecule and performs some of the roles attributed to CO. NO differs from CO in having a very short life-time due its high reactivity. Because of this, NO is pro-inflammatory; CO inhibits its production and is thus anti-inflammatory. NO is administered through NO-releasing compounds: Nitroprusside, [Fe(CN)5(NO)]2-, nitroglycerine and amyl nitrite have been used for well over 100 years and recently more NO-releasing molecules have been developed. They are now prescribed regularly to control blood pressure and to relieve angina.
The field of developing CORMs as pharmaceuticals is in its infancy. However, we should recapitulate that NO-releasing agents are very well established in medicine. Considering that the bioactive and pharmacological properties of CORMs were first described only five years ago and that there are already many reports of their beneficial application in animals, it can only be a matter of time before CORMs can be considered as a therapeutic stratagem in humans.
Read Mann and Motterlini's feature article 'CO and NO in medicine' in issue 41 of Chemical Communications.
Link to journal article
Also of interest
Developing iron nitrosyl complexes as NO donor prodrugs
Sandra A. T. Dillinger, Helmut W. Schmalle, Thomas Fox and Heinz Berke, Dalton Trans., 2007, 3562
1-2-Pyrone metal carbonyl complexes as CO-releasing molecules (CO-RMs): A delicate balance between stability and CO liberation
Ian J. S. Fairlamb, Jason M. Lynam, Benjamin E. Moulton, Ian E. Taylor, Anne K. Duhme-Klair, Philip Sawle and Roberto Motterlini, Dalton Trans., 2007, 3603