Modeling the Reactivity of .alpha.-Ketoglutarate-Dependent Non-Heme Iron(II)-Containing Enzymes

Abstract

a-Ketoglutarate-dependent Fe(II)-containing dioxygenase enzymes catalyze oxygenation of substrates by 0 2 with concomitant oxygenation and decarboxylation of the cofactor to produce COz and Recently Chiou and Que have reported two studies in which Fe(I1) complexes of benzoylformate (BF) were prepared and characterized as possible models for such enzyme^.^^^ Reaction of these complexes with 0 2 resulted in

Transition Metal Complexes and the Activation of Dioxygen

“…Yet only in a few cases has decarboxylation of the bound α-ketocarboxylate been accompanied by oxidation of a substrate in a reaction that would model enzyme function (Figure 32). In an early example, reaction of complex 62 with O 2 in the presence of cyclohexene or cis-stilbene resulted in decarboxylation of BF and formation of epoxides [226]. Complex 63a reacted with O 2 to yield a product in which the ortho position of one of the phenyl substituents was hydroxylated [227]; a similar intramolecular hydroxylation was observed for a phenylpyruvate analog (63b) [228].…”

Mechanism of Dioxygen Activation in 2‐Oxoglutarate‐Dependent Enzymes: A Hybrid DFT Study

“…Five-coordinate iron site: Since spectroscopic studies on CS [20,21] and model systems [32,36] have indicated that the iron complex must be five-coordinate to bind dioxygen efficiently, the five-coordinate complex, corresponding to species 3 in Scheme 1 and depicted in Figure 1B, has been chosen as a starting point for the calculations. The optimized structure of this species is shown in Figure 2, in which the spin population on iron and the most relevant interatomic distances are also presented.…”

“…This observation is in agreement with experimental data obtained for biomimetic complexes. [32,33] Once the transition state is passed, the electronic structure rearranges as the oxidative decarboxylation of a-KG supplies two electrons needed for the reduction of Fe 3 + ÀO 2 C À to the Fe 2 + ± peroxo species. The calculated free energy for this transition state is 16.1 kcal mol…”

“…Comparison of coordinatively saturated and unsaturated model systems has showed that the latter react with dioxygen much faster, demonstrating the importance of a vacant position at the ferrous ion. [31,32] In line with this experimental evidence, it has been proposed that dioxygen binds at this vacant position to iron and forms a ferrous-superoxo species (Fe 3 + ± O 2 C À ), which then performs a nucleophilic attack on the carbonyl carbon of the a-keto acid. The nucleophilic character of this reaction is supported by kinetic measurements performed for various derivatives with different substituents in the a-keto acid moiety.…”

“…In line with this argument there is experimental evidence showing that superoxide is a potent nucleophile [34] capable of cleaving a-keto carboxylic acids. [35] As the biomimetic complexes catalyze olefin epoxidation [32] and aryl hydroxylation, [36,37] the ferryl±oxo intermediate has been proposed to be responsible for the oxidative chemistry in these non-heme iron systems. Interestingly, such a ferryl±oxo non-heme iron species has recently been synthesized and characterized by Que, Jr. and co-workers.…”