Synthetic, kinetic and electrochemical aspects of ferrocene- and ruthenocene-containing titanium(IV) complexes with biomedical applications

[摘要] English: In this study, ruthenocene-containing β-diketones, ruthenocene-, cobalticenium- and/orferrocene- containing enaminones and ruthenocenyl and/or ferrocenyl containing titanium(IV)complexes were synthesised. Forty seven of these compounds were previously unknown.The keto-enol isomerization kinetics of the β-diketones RcCOCH2COR with R = C10F21,CF3, C6F5, C10H21, CH3, Rc and Fc have been studied by 1H NMR spectroscopy in CD3CN. Theinfluence of the solvent on this equilibrium has also been investigated utilising CD2Cl2 andCDCl3 as different solvents.The substitution reactions of the monodentate ferrocene-containing alkoxy groups of[Ti(O(CH2)nFc)2(RcCOCHCOCH3)2] {n = 1, 2, 3} with HO(CH2)nFc {n = 2, 3, 4} and thesubstitution of the bi-dentate β-diketonato ligand of [Ti(O(CH2)4Fc)2(RcCOCHCOR)2] {R=CH3, CF3} with RcCOCH2COR {R = CH3, CF3} is reported. Both revealed large positiveentropy values, which suggest a dissociative substitution mechanism.Electrochemical studies were conducted in dichloromethane in the presence of[NBu4][B(C6F5)4] as uncoordinating supporting electrolyte. All ruthenocene-containingcomplexes exhibited chemically and electrochemically irreversible behaviour for the Ru3+/Ru2+and Ti4+/Ti3+ couples. In contrast, the Fc/Fc+ couples were mostly found to be electrochemicallyquasi-reversible and chemically reversible. It was found that E01, Epa and Epc are dependent oneither the alkyl chain length of the ferrocene-containing alkoxy group or the groupelectronegativity of the R-group of the β-diketonato ligand in all complexes.Cytotoxic studies revealed that complexes [(C5H5)2Ti(RcCOCHCOR)]+ClO4,TiCl2(RcCOCHCOR)2 and Ti(O(CH2)4Fc)2(RcCOCHCOR)2, (R = C10F21, CF3, C6F5 or Fc),which contains more than one antineoplastic moiety, were the most effective in killing CoLo andHeLa cancer cell lines. These results are probably due to a synergistic effect between differentfragments possessing anti-cancer activity in the same molecule.Phase change studies of the complexes containing the long alkyl chains (R = C10H21,C10F21) and the crystal structure of [(C5H5)2Ti(RcCOCHCOCH3)]+ClO4 are also reported.

[发布机构] University of the Free State