Linear free-energy relationships and inverted Marcus region in the horseradish peroxidase-catalyzed oxidation of ferrocenes by hydrogen peroxide

Second-order rate constants (k(3)) for the steady-state horseradish peroxidase (HRP, isoenzyme C)-catalyzed oxidation of a variety of mono-, di (1,1')-, and pentamethyl ferrocenes by hydrogen peroxide into the corresponding ferricenium cations at 25 degrees C, pH 7 have been used to investigate steric and electronic effects on the reactivity in terms of the linear free-energy relationships (LFER) and the Marcus formalism for an outer-sphere electron transfer. There is a linear correlation with a negative slope between In k(3) and the formal redox potentials of ferrocenes (E degrees') for the mono- and di-substituted molecules suggesting that, in this series, k(3) increases with increasing the reaction driving force. The pentamethylated derivatives Cp*FeC(5)H(4)X, the E degrees' values of which are significantly lower compared with other ferrocenes, display markedly lower reactivity as to be anticipated based on LFER. This observation is rationalized by assuming that the great increase in the driving force for Cp*FeC(5)H(4)X is neutralized by the steric retardation imposed by the pentamethlyated cyclopentadienyl ring. The steric hindrance is believed to increase in the electron transfer distance from the organometallic donor to the heme of HRP which takes place on going from C(5)H(4)YFeC(5)H(4)X to Cp*FeC(5)H(4)X species. Alternatively, the reactivity trends reported can be accounted for in terms of the Marcus theory for the outer-sphere electron transfer, the Cp*FeC(5)H(4)X species being the spectators of the inverted Marcus region. (C) 1999 Elsevier Science S.A. All rights reserved.