Chemistry turns killer gas into potential cure

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Chemists at Sheffield University in the UK have discovered a way of using targeted small doses of carbon monoxide (CO), which could benefit patients who have undergone heart surgery or organ transplants and people suffering from high blood pressure.

Although lethal in large doses, small amounts of the gas can reduce inflammation, widen blood vessels, increase blood flow, prevent unwanted blood clotting, and suppress immune reactions to transplanted organs.

Research carried out in the last decade had already highlighted possible advantages, as CO is produced in the body as part of its own natural defensive systems. However, the problem has been finding a safe way of delivering the right dose of CO to the patient. Conventional CO inhalation can run the risk of patients or medical staff being accidentally exposed to high doses.

The researchers have developed water-soluble molecules which, when swallowed or injected, safely release small amounts of CO inside the human body.

The CO-releasing molecules (CO-RMs) have been developed in partnership with Roberto Motterlini at Northwick Park Institute for Medical Research in London, with funding from the UK Engineering and Physical Sciences Research Council.

“The molecules dissolve in water, so they can be made available in an easy-to-ingest, liquid form that quickly passes into the bloodstream,” says Brian Mann, from Sheffield’s Department of Chemistry, who led the research. “As well as making it simple to control how much CO is introduced into a patient’s body, it will be possible to refine the design of the molecules so that they target a particular place, while leaving the rest of the body unaffected.”

The CO-RMs consist of carbonyls of metals such as ruthenium, iron and manganese which are routinely used in clinical treatments. They can be designed to release CO over a period of between 30 minutes and several hours.

The technology is being further developed by hemoCORM Ltd, a spin-out company, which hopes to begin clinical trials within the next two years.