ETH Zurich: Carbon monoxide–releasing compounds for medical applications

Licensing opportunity

New rhenium-based compounds are available for license which release carbon monoxide in a controllable fashion, with the possibility to vary the carbon monoxide (CO) release half-life and to introduce targeting functions. The compounds are suitable for a variety of medical applications.

Carbon monoxide is recognised as a fundamental small molecule messenger in mammals. The endogenous production of CO is associated with the heme metabolic pathway, in particular the action of a family of enzymes known as heme oxigenases.

The tissue-specific distribution of heme oxigenases and, thus, the liberated CO have been linked to several physiological effects. For example, CO is a signalling molecule in the inducible defensive system against stressful stimuli; it has a fundamental role in the circulatory system, improving vasorelaxation and cardiac blood supply; it suppresses arteriosclerotic lesions associated with chronic graft rejection; like nitrogen oxide it influences neurotransmission in the hypothalamic pituary-adrenal axis.

ReII-based complexes have been discovered, which release carbon monoxide in a controllable and measurable fashion. The rate of CO release is pH-dependent with half-lives under physiological conditions varying from around 6 to 43 minutes. In comparison to other CO releasing molecules, these ReII-based complexes offer much broader possibility of tailoring for particular applications, for example in the introduction of targeting functions.

Preliminary experiments have shown that selected complexes exert a cytoprotective effect against hypoxia-reoxygenation in heart muscle cells. They would have applications in cardiovascular diseases, including cardiac hypoxia, cardiac infarction, cardiac hypertrophy and hypertension; ischaemia-reperfusion injury; inflammatory diseases; traumatic injury of the brain, kidney or liver; transplant rejection, platelet aggregation and/or monocyte activation; neuron degeneration of the nervous system and disorders of the circadian rhythm, for example, jet lag.

A patent has been applied for.