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

[摘要] 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 thetype [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 ofcomplexes, were determined using single crystal crystallographic techniques.Electrochemical studies were conducted in dichloromethane in the presence of [NBu4][B(C6F5)4] asuncoordinating 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 displayedirreversible electrochemistry while the Fc/Fc+ couple was electrochemically reversible. For the Ticomplexes, 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 andchemically reversible. In addition, for the mono-β-diketonato titanium(IV) salts, a splitting of theferrocenyl peaks was discernable. This phenomenon is exceptional. A unique monomer/dimerequilibrium was proposed as a possible explanation for this observation. Intra-molecularcommunication between the iron centres of [(FcCOCHCOPh)2Ti(Fc-CH(CH3)O)2] allowedelectrochemical detection of all four ferrocenyl centres.Cytotoxic studies revealed that complexes [Cp2Ti(FcCOCHCOR)]+ClO4-, which contain the titaniumand ferrocenyl antineoplastic moieties, were more effective in killing CoLo and HeLa cancer cell linesthan the parent titanocene dichloride compound which is currently in phase II clinical trials. Theseresults are attributed to a synergistic effect between different fragments possessing anti-cancer activityin the same molecule.

[发布机构] University of the Free State