Relationship between electrochemical potentials and substitution reaction rates of ferrocene-containing β-diketonato rhodium(i) complexes; Cytotoxicity of [Rh(FcCOCHCOPh)(cod)]

Abstract

A series of ferrocene-containing rhodium complexes of the type [Rh(FcCOCHCOR)(cod)] (cod = 1,5-cyclooctadiene) with R = CF₃, 1, (E_pa(Rh) = 269; E^o′(Fc) = 329 mV vs.Fc/Fc⁺), CCl₃, 2, (E_pa = 256; E^o′ = 312 mV), CH₃, 3, (E_pa = 177; E^o′ = 232 mV), Ph = C₆H₅, 4, (E_pa = 184; E^o′ = 237 mV), and Fc = ferrocenyl = (C₅H₅)Fe(C₅H₄), 5, (E_pa = 135; E^o′(Fc1) = 203; E^o′(Fc2) = 312 mV), have been studied electrochemically in CH₃CN. Results indicated that the rhodium(I) centre is irreversibly oxidised to Rh(III) in a two-electron transfer process before the ferrocenyl fragment is reversibly oxidized in a one-electron transfer process. The peak anodic (oxidation) potential, E_pa, (in V vs.Fc/Fc⁺) of the rhodium core in 1–5 relates to k₂, the second-order rate constant for the substitution of (FcCOCHCOR)⁻ with 1,10-phenanthroline in [Rh(FcCOCHCOR)(cod)] to form [Rh(phen)(cod)]⁺ in methanol at 25 °C with the equation lnk₂ = 39.5 E_pa(Rh) – 3.69, while the formal oxidation potential of the ferrocenyl groups in 1–5 relates to k₂ by lnk₂ = 40.8 E^o′(Fc)–6.34. Complex 4 (IC₅₀ = 28.2 μmol dm⁻³) was twice as cytotoxic as the free FcCOCH₂COPh ligand having IC₅₀ = 54.2 μmol dm⁻³, but approximately one order of magnitude less toxic to human HeLa neoplastic cells than cisplatin (IC₅₀ = 2.3 μmol dm⁻³).