Synthesis, structural aspects and electrochemistry of ferrocene-containing betadiketonato titanium(IV) complexes with biomedical applications

English: In this study ferrocene-containing β-diketones of the type [FcCOCH2COR] where R = Ph, CH3, CF3, Fc and Rc (Fc = ferrocenyl and Rc = ruthenocenyl) and β-diketonato titanium(IV) complexes of the type [Cp2Ti(FcCOCHCOR)]+ClO4 -, [(β-diketonato)2TiCl2] and [(β-diketonato)2Ti(Fc-CH(CH3)O)2] were synthesised. Eleven of these compounds were previously unknown. Complexes were characterised by 1H NMR spectroscopy and the structures of [RcCOCH2COFc] and [Cp2Ti(FcCOCHCOCH3)]+ClO4 -, as representative examples of two of the synthesised classes of complexes, were determined using single crystal crystallographic techniques. Electrochemical studies were conducted in dichloromethane in the presence of [NBu4][B(C6F5)4] as uncoordinating supporting electrolyte. Dimerization of the ruthenocenium fragment of the β-diketone [RcCOCH2COFc] was not as prominent as that of free ruthenocene. The Ru3+/Ru2+ couple displayed irreversible electrochemistry while the Fc/Fc+ couple was electrochemically reversible. For the Ti complexes, electrochemically quazi-reversible to irreversible behaviour was observed for the Ti4+/Ti3+ couple, while the Fc/Fc+ couples were mostly found to be electrochemically quasi-reversible and chemically reversible. In addition, for the mono-β-diketonato titanium(IV) salts, a splitting of the ferrocenyl peaks was discernable. This phenomenon is exceptional. A unique monomer/dimer equilibrium was proposed as a possible explanation for this observation. Intra-molecular communication between the iron centres of [(FcCOCHCOPh)2Ti(Fc-CH(CH3)O)2] allowed electrochemical detection of all four ferrocenyl centres. Cytotoxic studies revealed that complexes [Cp2Ti(FcCOCHCOR)]+ClO4 -, which contain the titanium and ferrocenyl antineoplastic moieties, were more effective in killing CoLo and HeLa cancer cell lines than the parent titanocene dichloride compound which is currently in phase II clinical trials. These results are attributed to a synergistic effect between different fragments possessing anti-cancer activity in the same molecule.