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Carbohydrate metal complexes as photo chemotherapeutics and radiotracers for the treatment and visualisation of cancer

Final Activity Report Summary - CARBOMETCOM (Carbohydrate metal complexes as photo chemotherapeutics and radiotracers for the treatment and visualisation of cancer)

The project was carried out to combine useful properties of carbohydrates and special metal complexes. Appending a carbohydrate has the ability to reduce toxicity, to improve solubility and opens up the possibility of molecular targeting of carbohydrate binding domains. Joined with special properties of selected metal complexes this should lead to materials with new features and novel kinds of application especially for the visualisation and treatment of cancer.

The first aim was to create sugar substituted ruthenium complexes in order to use the unique properties of this metal (fluorescence, photo activity, coordination behaviour etc.) for the design of novel photo chemotherapeutics. We succeeded to synthesise complexes with 'ball like' shape completely surrounded by different sugar residues. We could show that these compounds are able to produce singlet oxygen under irradiation. But the most remarkable result is that tests against different cell lines including cancerous cells show a significant differentiation between certain cells strongly depending on the character of sugar substitution. For future investigations this raises hope to find carbohydrate substituents which introduce a high selectivity for certain cells.

The second aim was to synthesise novel carbohydrate depending rhenium and technetium complexes and to study them as possible radiotracers for SPECT imaging. Two new types of Re and Tc complexes could be synthesised and structurally characterised. Experiments with the radioactive 99 mTc show the complete uptake of the nuclide and underline the high hydrophilicity of the formed compounds. Experiments concerning the stability of the formed complexes are still under investigation and the determination of a possible different distribution in tissue and body depending on the sugar substitution is considered.

Beside this we could develop practical synthesis routs towards carbohydrate depending tripodal silver complexes. These compounds were tested against several bacteria, fungi and yeasts. They show a broad range of effective antimicrobial activities. The use of the carbohydrate based substances enhances the antimicrobial activity and reduces the cytotoxicity and antiproliferative activity compared to the free silver(I) salts and makes them suitable for possible antimicrobial applications.