BIOACTIVE ORGANOMETALLIC COMPOUNDS
Sammanfattning: Various metal complexes have been used in medicine traditionally, although their use was often connected with mystery and with a lack of empirically (clinically) proven effect. In modern times, the development of biochemistry, bioinorganic and bioorganometallic chemistry allows us more in-depth understanding of biological action of metal containing substances. Among metal-containing drugs used today, platinum based drugs are the most common. Cisplatin, cis-Pt(NH3)2Cl2, is widely used in the clinic and it has contributed substantially to the success in treating cancer over the past three decades. However, therapy with Cisplatin often brings toxic side effects and development of drug resistance. In this thesis is presented a study of ferrocene- and ruthenocene-based bis-diphenylphosphines (with one phosphino-group on each cyclopentadienyl-ring) derivatised with an additional substituent on a metallocene ring. Synthesis, spectroscopic and electrochemical characterisation as well as X-ray crystal structure are described for some new metallocene-based phosphines and their platinum(II) and gold(I) complexes. Some of the new substances were tested for their ability to bind to sulfur-containing amino acids and selected oligonucleotides. Some complexes were even used in cytotoxicity and viral inhibition studies. These preliminary kinetic and biological studies reveal several promising candidate complexes of interest for further development.
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