Synthesis and functional evaluation of carbon monoxide releasing molecules (CORMs) and materials (CORMAs)

• Applicant: Professor Dr. Matthias Westerhausen, since 4/2018
• Subject Area: Biological and Biomimetic Chemistry ; Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2012 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 198096916

Carbon monoxide (CO) is a biologically important signaling molecule with beneficial medicinal properties. However, administration of gaseous CO is challenging due to its toxicity and, therefore, CO-releasing molecules (CORMs) are needed to administer CO at a predetermined location and time. Carbonyl complexes of iron, manganese and rhenium in low oxidation states allow administration of CO upon irradiation (photoCORMs). Such CORMs with novel functionalities, such as switchable solubility, luminescence and Raman reporters, will be synthesized. We expand our investigations towards metal complexes that show CO release also after oxidation of the metal complexes (redoxCORMs) or via ligand substitution reactions. In addition, inactive CORMs (iCORMs) will be generated for comparative reactivity and toxicity studies in order to separate the mode of action of CO, metal ions and coligands. Therefore, the mechanism of CO release will be investigated to identify side and end products. The underlying physico-chemical processes of CO release will be elucidated to design CORMs with improved properties with respect to targeting and CO release in order to use them in biological systems within FOR 1738. Close cooperation between members of the research unit ensures tuning of release properties via feedback loops. To minimize metal-based interactions, insoluble CORMs will be embedded in nonwovens yielding CO-releasing materials (CORMAs). Following a covalent immobilization strategy, polymerizable Yanus-head ligands will be used in 2nd generation CORMAs. They contain a metal binding unit as well as polymerizable side chains. After homopolymerization and insertion of metal carbonyl complexes novel light-triggerable CORMAs can be obtained as insoluble powders for highly efficient CO release with the metal ions remaining trapped in the polymer matrix. Sensing systems based on selective detection of the small signaling molecule CO via fluorescence and surface enhanced Raman spectroscopy (SERS) will be developed to quantitatively determine CO concentrations in aqueous media.

• DFG Programme: Research Units
• Subproject of: FOR 1738: Heme and Heme Degradation Products (HHDP): Alternative Functions and Signalling Mechanisms
• Ehemaliger Antragsteller: Privatdozent Dr. Alexander Schiller, until 3/2018