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 = CF(3), 1, (E(pa)(Rh) = 269; E(o)'(Fc) = 329 mV vs. Fc/Fc(+)), CCl(3), 2, (E(pa) = 256; E(o)' = 312 mV), CH(3), 3, (E(pa) = 177; E(o)' = 232 mV), Ph = C(6)H(5), 4, (E(pa) = 184; E(o)' = 237 mV), and Fc = ferrocenyl = (C(5)H(5))Fe(C(5)H(4)), 5, (E(pa) = 135; E(o)'(Fc1) = 203; E(o)'(Fc2) = 312 mV), have been studied electrochemically in CH(3)CN. 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 k(2), 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 lnk(2) = 39.5 E(pa)(Rh) - 3.69, while the formal oxidation potential of the ferrocenyl groups in 1-5 relates to k(2) by lnk(2) = 40.8 E(o)'(Fc)-6.34. Complex 4 (IC(50) = 28.2 μmol dm(-3)) was twice as cytotoxic as the free FcCOCH(2)COPh ligand having IC(50) = 54.2 μmol dm(-3), but approximately one order of magnitude less toxic to human HeLa neoplastic cells than cisplatin (IC(50) = 2.3 μmol dm(-3)).

The Relationship between the Electrochemical and Chemical Oxidation of Ferrocene‐Containing Carbonyl‐Phosphane‐β‐Diketonato‐Rhodium(I) Complexes – Cytotoxicity of [Rh(FcCOCHCOPh)(CO)(PPh3)]

“…Cell survival was measured by means of the colorimetric 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay and a cell survival curve as a function of concentration of 2 is shown in Figure 9. [32] These results are consistent with the betadiketonato ligand of 2 being responsible for most of the cell damage. The slightly higher activity of 2 as compared to the free ligand, FcCOCH 2 COPh, must arise in part from the presence of the toxic CO group in 2, but this is not the only reason.…”

“…The rhodium centre itself also exhibits neoplastic activity as demonstrated for the cod complex. [32] Results are interpreted to imply that the (CO)(PPh 3 ) ligand combination of 2 is not as amenable to cell internalization as linear or cyclic aliphatics such as cod. Also, the Rh metal-CO ligand combination will probably cause 2 to be scavenged in vivo by the body's defense mechanism, the macrophage from the reticuloendothelial system, thereby limiting its capability to gain access to neoplastic growths in vivo.…”

Reactivity of [Rh(β-diketonato)(cod)] complexes: A DFT approach

“…Electrochemical studies of ferrocene-containing b-diketonatocod rhodium complexes showed that the peak anodic (oxidation) potential of the rhodium core in [Rh(FcCOCHCOR)(cod)] (Fc ¼ ferrocenyl ¼ (C 5 H 5 )Fe(C 5 H 4 )) relates linear to lnk 2 , (k 2 the second-order rate constant for the substitution of 1,10-phenanthroline for (FcCOCHCOR) À in [Rh(FcCOCHCOR)(cod)] to form [Rh(phen)(cod)] þ in methanol at 25 C), the pK a of the bdiketone (FcCOCH 2 COR) and to the Gordy scale [25,55] group electronegativities of the substituent R [26].…”

Prediction of chemical and electrochemical oxidation potentials of β-diketonatobis(triphenylphosphite)rhodium(I) complexes: A DFT study

“…Various parameters can be used to describe the electronic effect of the substituent groups R and R 0 of which the pK a of the free b-diketone and the Gordy scale group electronegativities (v R + v R 0 ) are often used [21,22,[37][38][39][40][41][42].…”