Synthesis, electrochemical, kinetic and thermodynamic properties of new ferrocene-containing betadiketonato rhodium(I) complexes with biomedical applications

[摘要] English: Synthetic routes to prepare new ferrocene-containing β-diketones, FcCOCH2COR, with Fc =ferrocenyl, R = H, CH3, CH2CH3, CH(CH3)2 and C(CH3)3, have been developed. Rhodiumcomplexes of the type [Rh(FcCOCHCOR)(cod)] were obtained in yields approaching 80% bytreating these β-diketones with [Rh2Cl2-(cod)2]. Group electronegativities XR of R substituents weredetermined from a linear relationship between ethyl ester IR carbonyl stretching frequencies of thetype RCOOCH2CH3 and group electronegativities of known R groups. pKa values of new β -diketones were determined. 1H NMR studies on FcCOCH2COR indicated that enolisation in thedirection furthest from the ferrocenyl group always dominate. This finding is considered to be theresult of resonance driving force rather than inductive electronic effects of substituents on thepseudo-aromatic β-diketone core.Formal reduction potentials (Eol values vs. Ag/Ag+) of the iron core in the free β-diketones,FcCOCH2COR, and in [Rh(FcCOCHCOR)(cod)] complexes as well as the peak anodic oxidationpotentials, Epa, of the rhodium(I) nucleus were determined. The roles of pKa and group electronegativities on redox potentials are also discussed.Second-order rate constants, k2, for the substitution of the β-diketonato ligand, (FcCOCHCOR),from the complexes [Rh(FcCOCHCOR)(cod)] with 1,10-phenanthroline at 25°C in methanol weredetermined. Large negative values obtained for entropy of activation suggested an associativesubstitution mechanism. All substitution reactions were independent of a solvent step.Cytotoxic properties in terms of potential anticancer applications of these newly synthesised β- diketones and their rhodium complexes on cancer cells are described. Cytotoxicity was tested onHeLa, A2780 and A2780 platinum resistant cancer cells lines. Rhodium complexes were observed tobe more effective in killing cancer cells than the free β-diketones.

[发布机构] University of the Free State