Synthesis and electrochemistry of novel new ferrocene-containing water-soluble macromolecules with biomedical applications

The side effects associated with chemotherapy have caused an intensive research effort to find new ways of delivering a chemotherapeutic drug to a cancerous growth. One of these includes use of polymeric drug carriers. In this thesis is reported the syntheses, characterisation and electrochemistry of a series of antineoplastic ferrocene-containing amides and amines which was obtained from the corresponding ferrocene-containing carboxylic acids precursors. It is also described how the amines may be covalently anchored onto a water-soluble polymeric drug carrier to give the water-soluble ferrocene-containing polymers with biomedical applications. The influence of side chain length (i.e. the number of CH2 spacers) and type of the functional group (X = CONH2, NH2, NH3* and NHCO) on the ferrocenyl (Fc) formal reduction potential in compounds of the type Fc-(CH2)nX with n = 1- 4 is also highlighted. Cytotoxicity tests on all the amines. amides and polymers were investigated utilising HeLa, a human cervix epitheloid cancer cell line and CoLo DM320. an intrinsically multidrug resistant human colorectal cell line. Results showed that there exists a definite relationship between the length of the carbon chains linking the ferrocenyl antineoplastic moiety with either the polymer main chain ofNH2 and CONH2 functional group and effective cell death. Comparison of the cytotoxic results of the polymeric devices and monomeric antineoplastic ferrocene-containing amides and amines suggested that the benefits of a polymeric drug carrier is only observed in practice when the length of the side chain connecting drug and polymer main chain exceeds 5 atoms.